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Tour of a Human Cell I

This illustration simulates what we would see if we could K magnify a portion of a living cell by 1,500,000 times. At this H G magnication, atoms would be B about the size of a grain of salt, H cells would be the size of huge buildings, and you would be roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A , nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C C B C D G E G B The Machinery of Life E F F This image is taken from The Machinery of Life by David S. J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be used to explore the ultrastructure of cells, and X-ray B crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic © structure of molecules, and bioinformatics. © © Page 3 Nucleus. The nucleus is the cell’s library, storing the delicate strands of Pageare then processed: capping enzymes 13 (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteinsPage by looking for a special 7isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered Water Kit Flow of Genetic InformationDNA and protecting them from the rigors of theKit cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that Starter Kit the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real TM

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Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016 Version 1.1 - 2/2016

I Tour of a Human Cell Tour of a Human Cell I

This illustration simulates what This illustration simulates what K we would see if we could K we would see if we could magnify a portion of a living cell magnify a portion of a living cell by 1,500,000 times. At this H G magnication, atoms would be B by 1,500,000 times. At this about the size of a grain of salt, H H G magnication, atoms would be cells would be the size of huge B about the size of a grain of salt, buildings, and you would be roughly one-fourth the size of theH cells would be the size of huge earth in height, allowing you to J H buildings, and you would be walk across the continent in a few steps. All of the macromolecules roughly one-fourth the size of the in the cell are shown, including A earth in height, allowing you to proteins, nucleic acids, carbohy- B A I H J drates and lipid bilayers, but all of walk across the continent in a few the smaller molecules have been A D steps. All of the macromolecules omitted for clarity. In reality, the empty spaces in this picture are in the cell are shown, including lled with water, ions, sugars, ATP, A proteins, nucleic acids, carbohy- and many other small molecules. A B A D I drates and lipid bilayers, but all of The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated the smaller molecules have been to the production of antibodies. The entire process of antibody production is shown, starting from I G A D the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to omitted for clarity. In reality, the processing in the Golgi, and nishing with transport and secretion at the cell surface. C J empty spaces in this picture are C C lled with water, ions, sugars, ATP, B C D and many other small molecules. A G D E The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated G B to the production of antibodies. The entire process of antibody production is shown, starting from The Machinery of Life I G E the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to F F This image is taken from The Machinery of Life by David S. processing in the Golgi, and nishing with transport and secretion at the cell surface. C J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be J used to explore the ultrastructure of cells, and X-ray C B B C crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried C D molecules, but there is currently no way to observe G directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic E G structure of molecules, and bioinformatics. B E The Machinery of Life Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membraneF and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker Fantibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that This image is taken from The Machinery of Life by David S. wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. J Goodsell. It reveals a previously unseen level of F read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out A tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments biological scale. Light and electron microscopy may be ...where molecules become real TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane.

used to explore the ultrastructure of cells, and X-ray www.3dmoleculardesigns.com B crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics.

Tour of a Human Cell I Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layeredThis illustration nuclear simulates membrane what and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules K wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteinswe would see (I), if wewhich could carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) must also be edited by large spliceosome complexes (G) to remove intron regions membranemagnify is strengthened a portion of a living inside cell by criss-crossed layers of lamin protein laments (J). delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a cell in small transport vesicles. The protein clathrin (C) provides the molecular with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and by 1,500,000 times. At this endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of H The Golgi is the processing and sorting plant of the cell. Sugars and lipids are The cytoplasm of our cells is lled with enzymes and other proteins performing their G read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out magnication, atoms would be tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the manyB tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments about the size of a grain of salt, with transport proteins (A) that bind to ribosomes and guide new proteins inside as H collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real TM cells would be the size of huge buildings, and you would be cbm.msoe.edu roughly one-fourth the size of the 3dmoleculardesigns.com earth in height, allowing you to J H © © walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016 Version 1.1 - 2/2016 B Page 8 Page 5 proteins, nucleic acids, carbohy- Page 14 A I Daviddrates and lipid bilayers, but all of Goodsell Cellular Landscapes Enzymes in Action Kit Phospholipid & Membrane Transport Kit the smaller molecules have been A D omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C C B C D G E G B The Machinery of Life E Science Olympiad Protein Modeling Event Kits Page 23 F F This image is taken from The Machinery of Life by David S. J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be used to explore the ultrastructure of cells, and X-ray B crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics.

Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments ...where molecules become real TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane.

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Spring 2019 Product by Category

Water and Membrane Project-Based Learning Activities © © © Water Kit and NaCl Lattice ...... 3 Neurotransmitters Module: The Beery Twins’ Story © Channel Mini Models: Sodium Channel, Aquaporin Channel, Human Sepiapterin Reductase mRNA Gene Map and Mini Potassium Channel and Potassium Model and Dopamine and Serotonin Biosynthesis Models ... 18 Channel with Scorpion Toxin ...... 4 © Phospholipid & Membrane Transport Kit and Kits © © Phospholipid Modeling Set ...... 5 Water Kit ...... 3 © © Molecules of Life Collection ...... 12 Phospholipid & Membrane Transport Kit ...... 5 © ß-Globin Folding Kit ...... 6 © DNA Amino Acid Starter Kit ...... 7 © CRISPR/Cas9 Models ...... 10 Enzymes in Action Kit and © © Dynamic DNA Kit ...... 11 Substrate Specificity Kit ...... 8 © © Molecules of Life Collection ...... 12 Insulin mRNA to Protein Kit ...... 9 © © Flow of Genetic Information Kit and Dynamic DNA Kit ...... 11 © © Demo DNA Nucleotides ...... 13 Flow of Genetic Information Kit ...... 13 © © Ribosomes and Transfer RNA Mini Models ...... 16 Neuron Modeling Kit and Synapse Construction Kit ...... 19 © © DNA Starter Kit ...... 20 & Construction Kit and © DNA Starter Kit ...... 20 Amino Acids and Science Olympiad Protein Modeling Event Kits...... 23 © ß-Globin Folding Kit and ß-Globin Mini Models ...... 6 © Amino Acid Starter Kit , Amino Acid Models and Mini Models © Starter Kit Poster and Zinc Finger Mini Model ...... 7 Sodium Channel, Aquaporin Channel, Potassium Channel and © © Insulin mRNA to Protein Kit , Insulin Poster and Potassium Channel with Scorpion Toxin ...... 4 Insulin Mini Model ...... 9 ß-Globin ...... 6 © Molecules of Life Collection ...... 12 Zinc Finger ...... 7 © Genetic Codon Posters ...... 16 Acetylcholinesterase Active Site Cube ...... 8 Amino Acid Building Block Models ...... 19 Insulin ...... 9 Alpha Helix & Beta Sheet Models and Alpha Helix & Hemoglobin and CRISPR/Cas9 ...... 10 © Beta Sheet Construction Kit ...... 20 Nucleosome, Ribosomes and Transfer RNA ...... 16 Modeling Mini Toobers ...... 21 Antibody, Hemagglutinin and Influenza Virus Capsules ...... 17 Enzymes Dopamine and Serotonin Biosynthesis Models © Amino Acid Starter Kit ...... 7 and Sepiapterin Reductase ...... 18 © © Enzymes in Action Kit , Substrate Specificity Kit and Alpha Helix & Beta Sheet ...... 20 © Acetylcholinesterase Active Site Cube ...... 8 Green Fluorescent Protein ...... 21

ß-Globin Posters © © ß-Globin Folding Kit , ß-Globin Mini Models and Amino Acid Starter Kit Poster ...... 7 © © Map of the Human ß-Globin Gene ...... 6 Insulin Poster ...... 9 © © Hemoglobin Nylon Model and Poster ...... 10 Hemoglobin Poster ...... 10 © Genetic Codon Posters ...... 16 Practice of Science David Goodsell Cellular Landscapes: © © © © The Data Dilemma and Mystery Tube ...... 21 Tour of a Human Cell , Mitochondria Poster , Flu Fight: © © Immunity & Infection , E. coli Poster and Neuromuscular © Science Olympiad Protein Modeling Event Synapse Poster ...... 14 - 15 Pre-Build Kit and Practice Kit ...... 23

3D Molecular Designs utilizes magnets in many products to help students understand inter- and intra- molecular forces in the molecular world. In compliance with the Consumer Product Safety Improvement Act of 2008 - and California Proposition 65 - 3D Molecular Designs adds these warnings to our products and encourages the safe use of our products in classrooms and other science education settings. Our kits and models are science education products, not toys. Please contact us if you have any questions or concerns.

! WARNING: SMALL MAGNETS ! WARNING: CHOKING HAZARD CAUTION: This product contains small magnets. Swallowed magnets can stick This product contains small parts and should be kept out of the reach This is a science education together across intestines causing serious infections and death. Seek of children under the age of 3, because the parts or their pieces may product, not a toy. It is not intended immediate medical attention if magnets are swallowed or inhaled. present a choking hazard to small children. for children under 8 years old.

! WARNING: CALIFORNIA PROPOSITION 65 This product contains or may contain chemicals known to the State of California to cause cancer and/or birth defects or other reproductive harm. For more information visit www.P65Warnings.ca.gov.

2 ...where molecules become real TM

Water Kit©

While playing with these appealing magnetic water molecules your students will understand concepts that are often difficult to learn. They will explore hydrogen bonding, make ice, dissolve salt, evaporate water, explore transpiration, © create ethanol and much more. Each Water Kit cup includes pieces for 12 water © molecules, 1 sodium, 1 chloride, 1 ethane and 1 hydroxyl group. All atoms are correctly magnetized to reflect their positive or negative charges. Lessons and activities are available online at 3dmoleculardesigns.com/Teacher-Resources.htm. Water Kit Water 10-Cup Set $399 (WK-10) • 8-Cup Set $328 (WK-08) 6-Cup Set $249 (WK-06) • 1-Cup $44 (WK-01)

Also see Aquaporin Channel Mini Model (page 4) and Phospholipid & Membrane Transport Kit© (page 5).

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product 3D Water Makes Learning Sensational! ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details.

© Use the Water Kit and NaCl together! NaCl Lattice 4x4x4 Lattice

Your students will discover the cubic nature of salt crystals, efficient lattice packing, high melting temperature, brittleness, cleavage planes and more with these models. Each ion model has 6 embedded magnets to simulate ionic © bonding. The 4x4x4 lattice contains 64 ions - 32 sodium and 32 chloride. The 3x3x3 lattice contains 27 ions - 13 of 1 type of ion and 14 of the other. (Water molecules are not included.) 4x4x4 Lattice $177 (NACL-04)

3x3x3 Lattice $82 (NACL-03) Lattice NaCl Also see Sodium Channel and Potassium Channel Mini Models (page 4). 3x3x3 Lattice

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details.

3dmoleculardesigns.com 3 ...where molecules become real TM

Spring 2019 Channel Protein Mini Models Sodium Channel Mini Model Sodium Channel Channel Sodium

Mini Model Mini This model of a bacterial sodium channel shows the pore domain of the protein. The pore domain is a homo-tetramer in which 4 identical proteins come together to form the ion pore — exposed on the outside surface of the cell. The protein structure was captured in its open conformation, where your students can easily see how hydrated Na+ ions can be released into the cytoplasm after passing through the pore. ! WARNING: CHOKING HAZARD CAUTION: Science Education Product 3.75” Plaster Model $101 (SCMM) ! WARNING: CALIFORNIA PROP 65 © © Also see Water Kit and NaCl Lattice (page 3). Please see bottom of page 2 for details.

Aquaporin Channel Channel Aquaporin Aquaporin Channel Mini Model Mini Mode Mini Aquaporin — a membrane-spanning protein — is responsible for moving water across a lipid bilayer. Its structure consists of 6 alpha helices and 2 half alpha helices that form an hourglass shape through which water molecules move one at a time. Two asparagine amino acids located near the center of the hourglass function to selectively allow only water molecules to pass through. l 3.75” Plaster Model $84 (ACMM) Also see Water Kit© (page 3).

The Aquaporin Mini Model opens to ! ! show water molecules rolling over in their WARNING: CHOKING HAZARD WARNING: SMALL MAGNETS CAUTION: Science Education Product passage through the channel. ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Potassium Channel Mini Model Potassium Channel

Mini Model Mini The potassium channel is a 4-subunit, transmembrane protein that allows the rapid passage of potassium ions — but not sodium ions — across the membrane. The protein backbones of the 4 subunits form a channel, with carbonyl oxygen atoms precisely positioned in 3-D space to replace the water that normally hydrates each ion. Since there is no energetic difference between a hydrated potassium ion and the same ion bound in the pore of the potassium channel, the ion rapidly passes through the channel in a frictionless manner. 3.75” Plaster Model $105 (PCMM) Also see NaCl Lattice© (page 3).

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Potassium with Channel Bound Scorpion Toxin Model Mini Potassium Channel Bound with Scorpion Toxin Mini Model

These 2 models enable you to tell many stories. The green potassium channel model illustrates how this amazing protein allows the rapid transport of potassium channel ions while simultaneously preventing the flow of smaller sodium ions. The yellow scorpion toxin model (from the Chinese scorpion Buthus martensi) shows how disulfide bonds stabilize the structure of this small protein, how some proteins interact to form multi-protein complexes and how a strategically placed lysine side chain of the magnet-docked scorpion toxin plugs the channel through which potassium ions normally flow. 5” Plaster Model $145 (PCSMM)

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

4 Channel protein mini models are built at the same scale. They are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM

Phospholipid & Membrane Transport Kit©

Let your students discover the spontaneous formation of membranes for themselves, using this kit featuring the amphipathic structure of phospholipids, with their hydrophilic heads and hydrophobic tails. Your students will explore © the chemical structure of a phospholipid and then construct a phospholipid monolayer, micelle and bilayer, leading to an understanding of the plasma membrane structure. Additional components of this kit allow students to construct lipid bilayers and consider the role of transport proteins in moving ions and small molecules across membranes. Lessons and activities are available online at 3dmoleculardesigns.com/Teacher-Resources.htm. Kit Transport 1-Group Set $38 (PMTK-01) 3-Group Set $99 (PMTK-03) Also see Water Kit© (page 3). Phospholipid & Membrane

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details.

Phosphorylated Na+/K+ Pump Phospholipid Structure

Phospholipid Modeling Set Use these models together!

® These Molymod phospholipid models enable your students to explore the amphipathic © structure of phospholipids, the most abundant lipids in membranes. The set contains all of the atoms and bonds needed to construct five phospholipids and compare and contrast the chemical make-up of their hydrophilic heads and hydrophobic tails. The phospholipid models can be used separately or with the Phospholipid & Membrane Transport Kit©. Phospholipid Modeling Set $249 (PLMS-01) • Phosphatidylcholine $60 (PLMS-A) Phospholipid

Phosphatidylserine $58 (PLMS-B) • Phosphatidylinositol $63 (PLMS-C) Modeling Set Phosphatidylethanolamine $56 (PLMS-D) • Sphingomyelin $62 (PLMS-E) Indicates Double Bond

Also see Water Kit© (page 3) and Phospholipid & Membrane Transport Kit© (above).

! WARNING: CHOKING HAZARD CAUTION: Science Education Product Please see bottom of page 2 for details.

Phosphatidylinositol Phosphatidylcholine Sphingomyelin Phosphatidylethanolamine Phosphatidylserine

3dmoleculardesigns.com 5 ...where molecules become real TM

Spring 2019 β-Globin Folding Kit© β-Globin Folding Kit β-Globin Proteins become real in your students’ hands as they fold 3 mini toober β-globin fragments and discover the primary, secondary and tertiary structure in this model. Maps guide your students in folding the mini toobers into β-globin’s 3-D shape. Use the folded mini toober model of β-globin to discuss protein structure, the important role of hemoglobin in oxygen transport and the lasting effects of a single amino acid on a protein. The kit includes mini toobers, folding map guides, amino acid side chains, heme group, iron atom, oxygen atoms and an assortment of parts to mark and connect the fragments. The folding kit can be used successfully by 6 to 9 students working in 3 teams. ! WARNING: CHOKING HAZARD © Lessons and activities are available online at Folding Kit $134 (BGFK) ! WARNING: SMALL MAGNETS 3dmoleculardesigns.com/Teacher-Resources.htm. CAUTION: Science Education Product It’s best if your students first use the Amino Acid Starter Kit© (page 7) before using the ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details. β-Globin Folding Kit©. Also see Map of the Human β-Globin Gene© (below).

Mini Model Mini β-Globin Mini Model β-Globin β-Globin Use this β-Globin Mini Model as an accurate, smaller-scale template for the β-Globin Folding Kit©. The model features the heme group with its iron atom which binds oxygen; the location of the sickle cell mutation; and selected charged, hydrophobic and hydrophilic side chains. The 3 colors correspond to the 3 fragments in the kit. 4” Plaster Model $92 (BGMMFK)

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Map of the Human β-Globin Gene© AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT A 3DMD Paper BioInformatics Activity© 62000 62050 62100 62150 62200 62250 62300 62350 62400 62450 62500 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63100 63150 63200 63250 63300 63350 63400 63450 63500 63550 63600 63650 63700 63750 β-Globin mRNA 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+---A ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 -75 CAAT Box -25 TATA Box begins here. EXON I + EXON II T A A A Reduced level of β-Globin protein is made due to inefficient donor splice site (β thalassemia). © TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTG T AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACATAAAAGTCAGGGCAGAGCCATCTATTGCTTTCCTCTTCAGA C GACGATCTTGACTATCTGAGCACAAACCTGTGTTGCACATACGCAACCTCAACACCAGAGCATCCATTGCGTGCCACCCTGATCTTCCTGGACGGAGACAGCTCTGCACGTCTATCTGTCCCACTGTGAGGCGCACAGAGTGCAACGTAGGCATTGAACGTCTGGTGGTGAGAGCCCTCGGCGCAGGGTTGCGTCATCAAAGGCTTACCAAGATCAAGGTGTTTAATGGACGACCAATAGATAAGCTTGGGTCACTGTGGGAGATCACGAGCAAGAACTCATTTGGGTTTCTCTCGATACGGCTACGTGAGCTTTCTCTCATGCTCTCATTGGTTCTATGTTATCCCACCCCTTGAGTGCTAGCCTGGATGCGTCTATCCCTTGGGACCTCACGAGTGTCTCTTTGACGTCTCTGTTGAGGGAATCTAGTCCACCTCCTAGAATGCATGTTATGCGGTCAACCTCTCAAGCGTGAATGGGCTCAATCGGCTAAGGAAAGTGAGCTCGGATGCGCTATTCAGTGGAGTGGACCTGGACTACACCTCGGACAGACACTCTAAAGGGACAACCATTTGGCGCACGACTGAGGTGAGCTAGCACTGTCGACAAGCTAGCACGTGAGACTCCTGAGACACCTTACAGGGATGATGTGCTAGTGGGACCACTCTGACTGTTTGTCGTTTGCCTCCCTTTCTTCTTCTAATGGATTGAAAGTTACAATGTCCATAGCGAAGGGGAGAAGATAACACGGCGTACCACGTTTAGAGATGAGGCAAACAGAGCGATATGATATGGCATGCAAGTGCTGTGAAGTCCTGCAGAGACTCGATTATTTAGTATTCTTCTTCATTGTGTCTGTTTGCAGTAAGCAATTGTTTTCCCTTTATGTCTTTAATTCCTTGCCTGTTACTTGTTTTTATTCTTCCTGCCGTCATATCTTTTATCTATTTCATACTCTAGATGACCGTTACACCATTAGTCGTAGTAGACAAAAGAGAATATCATCATCCTGATGATACATCTAGAGTGAAACTTCAACAAGAAAAAGCTTTAGCACGAGATCCTGCCTTAGTGTACATTACGTATGTTAGGGAATATTATGCTGCTGCTTGATTTGCAGTATATCATAATCTCGCCGTATCTTGTATTTGTCATTTCTATTCTTTAAACTTGTATCACAGTAATCATGTATACGATATTCTAATGGCGTTAGAAGTTGTAACTGGTTTATACATGATGTTGGTACACATACTTCGACTCAAGAATCAGGGAGTACATTTTCGCTATTTGTAATTATTGAAATAACATCGCTCTTACTTCCTTTTCAAATATGACATTTTTATGCTTTCATCTTATGTTGCTAGATACTATTCCCTTAATCTCATTATCTATTACAGGGACAATAAATGATGACGAATGGTATCAATGCACTCATTATGCAACGCATATCTATAAAGCAACTAACAAGTGTATTAATCTTACTAGGGTTTAAGAGCCAATAAGGCAATTATTTCTCGCCATATTATAACTATCTTCTGCCATATCAATATTGTCAAACTGTATTGTAGAGTAGGCTTCTCCATATTTGCTGAATAGCCAAGCTAACAAATCCAGTCTATCCATTCCTCGCCTTTTATTTTAGTTGGTTCGGTGATGAACGGCTTGTGATATACTTCTTGAAGATCCAAGCTAGAGCCGCTTTCTGCATACATCAATCGTTCCATACTCTCCTATATGCTATCCGTCTCCACCACGCTCCATGGGCAAACGTAGCATGAGTCTTGCTGTAGCATGGACCGCATACACTATTGAGCTAAAGAATTACACCCGCCACCCAAGTGCAGGCTTGCACTATTCTAGAGAATGTGTGTAGGCATGCGTAGTGAGCATAATGGCCCATGAGCACCACACAGTAATACACATATAGCTTCAGCATTTGCTATGCATGCTCCGAAATTATCTAATGTAAAGAGTTACCATTATGTATCACCTAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 Don’t just tell your students about triplet codons, reading frames or 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+ Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATT Acceptor Splice Site Map of the Human of the Human Map Donor Splice Site INTRON I

Version 2.4 Version introns and exons. Let them discover these eukaryotic gene features 3 Forward a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D T T V F T S N L K Q T P W C T * L L R R S L P L L P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S 50T P D A V M G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V Human β-Globin Gene on Chromosome 11 a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D reading T b TA S AV R R FA K DT R Y S G C HN H L L D L KT L W Q S H TT L GP L A WN L LC P G T A G *R A G L A R LA G HR K S RQ G RS A I L Y C LP H L L L L LT Q L P C S CL A TG S N AR H HR G A * P D ST * G W E V MC R Y K C P LV G QV G E VR G *R S W P W * GW P G A Q V G I K W V T YR Q VQ * G G D Q *Y K L K G M TW R Q G R R LL L GR F * R* A LP T L I S A YE W S T I F GP P LH G C VW W SE T L T G P RE G S K L S TP L G L I C GP L LF M L LL W AI T L G R * TR L M D A R SK C SL V P CL V ML A W L L T WV T T Y S R FA P LP P H T* V SL C T R V T SL C T L W I VL R T V S G Y* V YP G T WL D VT F F Q P L RL F Y F G * FV H VE I G SR G EF V T G G Y SD L E L W E ST D E T * L PH Q CD G S A L R IV V L M V S GF I C N C S P* Q LK F S VF V *K F L A L S FH F F G F S KA I F K T I VI L NL A L G T L CA I T F K G SN I S D E I GH * VL T * AK K TH L H L S L DP S T N L L LF G IK Y V GC L FT A Y F S * SA P Y T F I LF F Y S F * EL I HL N H H Y T YC L W D V K KV * C L F N HM C TV H I DD Q IP R V E I L HN L * F F * RK M LV S S SF N IL L F W C L SD Y F P * Y *F P * C S L FS F RL A I S M I QP C I S M P FL C T L I L WK N NL S D SN F WS V K C A I AH I F R L H KI N IG S A RY K LS * L N M * ER V S V Y C Q* * Q F L Q RS S YM H S G A F IN L W R L G R* G W M I I IL S PA S * SA L LV L I W M F IK P L S I F QL P QD L L RG N VF L V S C V LF A H F H F YG K E L F T LP P VF Q A IA Y QT K V I V A VG V A F N A FL A HC K Y LH * AI R F L L A VA Q F F L L FK V P F L F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T

β-Globin Gene β-Globin frames Student Copy Student © c P V P E E P R T G T A V I T * T S P C G A T P * G W P I Y S Q E Q G G Q E P G L G I K V R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C 1 2 3 4 5 6 7 8 9 10 20 30 Consensus Consensus Globin Gene Map Copyright 2013 3D Molecular Designs, LLC β Consensus Consensus EXON INTRON INTRON EXON b A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L H L L L T Q L C S L A T S N R H H GC A P D S TATA* Box GTATA A AET V C R Y C PThe first methionineV aminoG acid isQ G E R G * S W W * G P G Q V GNote: all intronsI begin K with andV end withT RDonor SpliceQ Site V * G DAcceptor SpliceQ Site * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L - CAAT Box GG( )CAATCT ( T ) (A ) cleaved from the β-Globin protein This negatively charged GU AG. as they explore the Map of the Human -Globin Gene . Starting Promoter Region T V C A TM www.3dmoleculardesigns.com soon after its synthesis. glutamic acid (E) is AG GU YYYYYYYYYNCAG G β ...where molecules become real c P V P E E P R T G T A V I T * T S P C G A T P * G W withP I theY S protein Q E Q sequence,G G Q E P students G L G I work K V backwardR A E P S to I discover A Y I C the F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G Kreplaced byV a hydrophobic N valine V(V) in sickle D cell anemia. E V G G E A L G R L V S R L Q D R FA KG E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * β -globin gene. Student maps can be used by individuals or small The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β+ thalassemia). Sickle Cell Anemia + Hemoglobin Shepherds Bush Hemoglobin Shanghai Transcription continues Erythroid Specific Promoters β-Globin mRNA No β-Globin protein is made due to non-functional donor splice site (β0 thalassemia). Splicing Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β thalassemia). Hemoglobin Hiroshima groups and are available in sets of 1, 3 or 12. One teacher’sbegins map here. A Polyadenylation Polyadenylation Site GT - Rich for 200 - 300 nucleotides. -75 CAAT Box -25 TATA Box EXON I β- β+ EXON II EXON III C Signal Region comes with every combo. The teacher’s map features highlighted T A A A Reduced level of Globin protein is made due to inefficient donor splice site ( thalassemia). A G A 3DMD Paper BioInformatics Activity© AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 62500 62540 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63100 63150 63200 63250 63300 63350 63400 63450 63500 63550 63561 63600 63650 63700 63750 © 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------reading frames and mutation sites. ---+------+------+------All maps are laminated. ---+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA Teacher notes, instructions and student handouts are available Donor Splice Site INTRON I Acceptor Splice Site INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II

Version 2.4 Version Human β-Globin Gene on Chromosome 11 ©

Teacher Copy Teacher online at 3dmoleculardesigns.com/Teacher-Resources.htm. Copyright 2013 3D Molecular Designs, LLC a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D T T V F T S N L K Q T P W C T * L L R R S L P L L P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S T P D A V M G N P K V60 K A H G K K V L G A F S D G L A H L D 80N L K G T F A T L S E L H C D K L H V D 100P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T Globin Gene Map 3 Forward 50 70 90

- www.3dmoleculardesigns.com TM reading b H L L L T Q L C S L A T S N R H H G A P D S * G E V C R Y C P V G Q G E R G * S W W * G P G Q V G I K V T R Q V * G D Q * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L β A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L 120 K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L ...where molecules become real frames 110 130 140 c P V P E E P R T G T A V I T * T S P C G A T P * G W 1P Student I Y S Qand E Q1 TeacherG G Q E Map P G ComboL G I K$40 V (BGGM-01S-01T)R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * Consensus 1 2 3 4 5 6 7 8 9 10 20 30 Consensus Consensus Consensus A T The first methionine amino acid is EXON INTRON INTRON EXON Replacing histidine (H) with aspartic acid (D) CAAT Box3 StudentGG C CAATCT and 1 Teacher Map TATACombo Box TATA$60( (BGGM-03S-01T)) A( ) Note: all introns begin with and end with Donor Splice Site Acceptor Splice Site D The average length of the 53 ORFs (Open Reading Frames) in Intron II is 15 codons. P D ( T ) T A cleaved from the β-Globin protein This negatively charged GU AG. Negative charge introduced into BPG binding site. Proline disrupts the alpha helix and eliminates a salt bridge to the alpha chain Promoter Region V C A YYYYYYYYYNCAG The longest ORF in this intron is 73 codons (62653-62871). 12 Student and 1 Teacher Map Combo $162 (BGGM-12S-01T) soon after its synthesis. glutamic acid (E) is AG GU G Reduced BPG binding results in increased O2 affinity. results in unstable hemoglobin. and eliminates the Bohr effect. replaced by a hydrophobic valine (V) in sickle cell anemia. A G

+ Sickle Cell Anemia The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β thalassemia). Hemoglobin Shepherds Bush Erythroid Specific Promoters β-Globin mRNA 0 Splicing Mutations Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β+ thalassemia). Hemoglobin Shanghai Hemoglobin Hiroshima Transcription continues No β-Globin protein is made due to non-functional donor splice site (β thalassemia). A Polyadenylation GT - Rich for 200 - 300 nucleotides. -75 CAAT Box -25 TATA Box begins here. EXON I + EXON II EXON III Polyadenylation Site T A A A Reduced level of β-Globin protein is made due to inefficient donor splice site (β thalassemia). A C G Signal Region © β-Globin Mini Model A 3DMD Paper BioInformatics Activity AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT 62000 62050 Model Mini 62100 62150 62206 62265 62279 62283 62300 62350 62388 62540 63100 63150 63200 63250 63300 63350 63400 63450 63561 63650 63700 63750 © 62200 62250 62400 62450 62500 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63500 63550 63600

61981 ------+------+------+------+------+------+------+------+------+------+------+------+------β-Globin ---+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGβTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA The side chains on this -Globin Mini Model indicate noted mutations on the Donor Splice Site INTRON I Acceptor Splice Site INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II Version 2.4 Version Human β-Globin Gene on Chromosome 11 β © Teacher Copy Teacher Copyright 2013 3D Molecular Designs, LLC a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q Teacher S H L L Map L T of F theA S Human D T T V -Globin F T S NGene L K Q. It T also P W features C T * L the L hemeR R S groupL P L withL P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S T P D A V M G N P K V60 K A H G K K V L G A F S D G L A H L D 80N L K G T F A T L S E L H C D K L H V D 100P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T Globin Gene Map 3 Forward 50 70 90

- www.3dmoleculardesigns.com TM reading b H L L L T Q L C S L A T S N R H H G A P D S * G E V C R Y C P V G Q G E R G * S W W * G P G Q V G I K V T R Q V * G D Q * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L β A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L 120 K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L ...where molecules become real frames its iron atom which binds oxygen. The 3 colors of the alpha carbon backbone 110 130 140 c P V P E E P R T G T A V I T * T S P C G A T P * G W P I Y S Q E Q G G Q E P G L G I K V R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * Consensus 1 2 3 4 5 6 7 8 9 10 20 30 Consensus Consensus Consensus A T correspond to the 3 exons in theThe first gene. methionine amino acid is EXON INTRON INTRON EXON Replacing histidine (H) with aspartic acid (D) CAAT Box GG C CAATCT TATA Box TATA ( ) A( ) Note: all introns begin with and end with Donor Splice Site Acceptor Splice Site D The average length of the 53 ORFs (Open Reading Frames) in Intron II is 15 codons. P D ( T ) T A cleaved from the β-Globin protein This negatively charged GU AG. Negative charge introduced into BPG binding site. Proline disrupts the alpha helix and eliminates a salt bridge to the alpha chain Promoter Region V C A YYYYYYYYYNCAG G The longest ORF in this intron is 73 codons (62653-62871). 4” Plaster Model $92 (BGMMPBI) soon after its synthesis. glutamic acid (E) is AG GU Reduced BPG binding results in increased O2 affinity. results in unstable hemoglobin. and eliminates the Bohr effect. replaced by a hydrophobic valine (V) in sickle cell anemia. A G ! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β+ thalassemia). Please see bottom of page 2 for details. Sickle Cell Anemia + Hemoglobin Shepherds Bush Erythroid Specific Promoters β-Globin mRNA 0 Splicing Mutations Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β thalassemia). Hemoglobin Shanghai Hemoglobin Hiroshima Transcription continues No β-Globin protein is made due to non-functional donor splice site (β thalassemia). A Polyadenylation GT - Rich for 200 - 300 nucleotides. -75 CAAT Box -25 TATA Box begins here. EXON I + EXON II EXON III Polyadenylation Site T A A A Reduced level of β-Globin protein is made due to inefficient donor splice site (β thalassemia). A C G Signal Region A 3DMD Paper BioInformatics Activity© AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 62500 62540 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63100 63150 63200 63250 63300 63350 63400 63450 63500 63550 63561 63600 63650 63700 63750 © 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA 6 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. Donor Splice Site INTRON I Acceptor Splice Site INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II

Version 2.4 Version Human β-Globin Gene on Chromosome 11

Teacher Copy Teacher Copyright 2013 3D Molecular Designs, LLC a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D T T V F T S N L K Q T P W C T * L L R R S L P L L P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S T P D A V M G N P K V60 K A H G K K V L G 70A F S D G L A H L D 80N L K G T F A T L S 90E L H C D K L H V D 100P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T Globin Gene Map 3 Forward 50

- www.3dmoleculardesigns.com TM reading b H L L L T Q L C S L A T S N R H H G A P D S * G E V C R Y C P V G Q G E R G * S W W * G P G Q V G I K V T R Q V * G D Q * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L β A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L 120 K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L ...where molecules become real frames 110 130 140 c P V P E E P R T G T A V I T * T S P C G A T P * G W P I Y S Q E Q G G Q E P G L G I K V R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * 1 2 3 4 5 6 7 8 9 10 30 Consensus Consensus 20 Consensus EXON INTRON Consensus C A T The first methionine amino acid is Use with Map of the Donor Splice Site Acceptor Splice Site INTRON EXON The average length of the 53 ORFs (Open Reading Frames) in Intron II is 15 codons. Replacing histidine (H) with aspartic acid (D) CAAT Box GG CAATCT TATA Box TATA ( ) A( ) © Note: all introns begin with and end with D P D ( T ) T A cleaved from the β-Globin protein This negatively charged β GU AG. Negative charge introduced into BPG binding site. Proline disrupts the alpha helix and eliminates a salt bridge to the alpha chain Promoter Region V Human -Globin Gene C A YYYYYYYYYNCAG The longest ORF in this intron is 73 codons (62653-62871). soon after its synthesis. glutamic acid (E) is AG GU G Reduced BPG binding results in increased O2 affinity. results in unstable hemoglobin. and eliminates the Bohr effect. replaced by a hydrophobic valine (V) in sickle cell anemia. A G

+ Sickle Cell Anemia The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β thalassemia). Hemoglobin Shepherds Bush Erythroid Specific Promoters β-Globin mRNA 0 Splicing Mutations Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β+ thalassemia). Hemoglobin Shanghai Hemoglobin Hiroshima Transcription continues No β-Globin protein is made due to non-functional donor splice site (β thalassemia). A Polyadenylation GT - Rich for 200 - 300 nucleotides. -75 CAAT Box -25 TATA Box begins here. EXON I + EXON II EXON III Polyadenylation Site T A A A Reduced level of β-Globin protein is made due to inefficient donor splice site (β thalassemia). A C G Signal Region A 3DMD Paper BioInformatics Activity© AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 62500 62540 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63100 63150 63200 63250 63300 63350 63400 63450 63500 63550 63561 63600 63650 63700 63750 © 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA Donor Splice Site INTRON I Acceptor Splice Site INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II Version 2.4 Version Human β-Globin Gene on Chromosome 11

Teacher Copy Teacher Copyright 2013 3D Molecular Designs, LLC Globin Gene Map 3 Forward a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D T T V F T S N L K Q T P W C T * L L R R S L P L L P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S 50T P D A V M G N P K V60 K A H G K K V L G 70A F S D G L A H L D 80N L K G T F A T L S 90E L H C D K L H V D 100P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T - www.3dmoleculardesigns.com reading β TM b A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L H L L L T Q L C S L A T S N R H H G A P D S * G E V C R Y C P V G Q G E R G * S W W * G P G Q V G I K V T R Q V * G D Q * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V L V C V L A H H F G 120K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L ...where molecules become real frames 110 130 140 c P V P E E P R T G T A V I T * T S P C G A T P * G W P I Y S Q E Q G G Q E P G L G I K V R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * Consensus 1 2 3 4 5 6 7 8 9 10 20 30 Consensus Consensus Consensus A T The first methionine amino acid is EXON INTRON INTRON EXON Replacing histidine (H) with aspartic acid (D) CAAT Box GG C CAATCT TATA Box TATA ( ) A( ) Note: all introns begin with and end with Donor Splice Site Acceptor Splice Site D The average length of the 53 ORFs (Open Reading Frames) in Intron II is 15 codons. P D ( T ) T A cleaved from the β-Globin protein This negatively charged GU AG. Negative charge introduced into BPG binding site. Proline disrupts the alpha helix and eliminates a salt bridge to the alpha chain Promoter Region V C A YYYYYYYYYNCAG G The longest ORF in this intron is 73 codons (62653-62871). soon after its synthesis. glutamic acid (E) is AAG GU Reduced BPG binding results in increased O2 affinity. results in unstable hemoglobin. and eliminates the Bohr effect. replaced by a hydrophobic valine (V) in sickle cell anemia. G

+ Sickle Cell Anemia The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β thalassemia). Hemoglobin Shepherds Bush Erythroid Specific Promoters β-Globin mRNA 0 Splicing Mutations Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β+ thalassemia). Hemoglobin Shanghai Hemoglobin Hiroshima Transcription continues No β-Globin protein is made due to non-functional donor splice site (β thalassemia). A Polyadenylation GT - Rich for 200 - 300 nucleotides. -75 CAAT Box -25 TATA Box begins here. EXON I + EXON II EXON III Polyadenylation Site T A A A Reduced level of β-Globin protein is made due to inefficient donor splice site (β thalassemia). A C G Signal Region A 3DMD Paper BioInformatics Activity© AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 62500 62540 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63100 63150 63200 63250 63300 63350 63400 63450 63500 63550 63561 63600 63650 63700 63750 © 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA Donor Splice Site INTRON I Acceptor Splice Site INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II

Version 2.4 Version Human β-Globin Gene on Chromosome 11

Teacher Copy Teacher Copyright 2013 3D Molecular Designs, LLC a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D T T V F T S N L K Q T P W C T * L L R R S L P L L P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S T P D A V M G N P K V60 K A H G K K V L G A F S D G L A H L D 80N L K G T F A T L S E L H C D K L H V D 100P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T Globin Gene Map 3 Forward 50 70 90

- www.3dmoleculardesigns.com TM reading b H L L L T Q L C S L A T S N R H H G A P D S * G E V C R Y C P V G Q G E R G * S W W * G P G Q V G I K V T R Q V * G D Q * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L β A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L 120 K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L ...where molecules become real frames 110 130 140 c P V P E E P R T G T A V I T * T S P C G A T P * G W P I Y S Q E Q G G Q E P G L G I K V R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * Consensus 1 2 3 4 5 6 7 8 9 10 20 30 Consensus Consensus Consensus A T EXON INTRON INTRON EXON Replacing histidine (H) with aspartic acid (D) CAAT Box GG C CAATCT TATA Box TATA ( ) A( ) The first methionine amino acid is Note: all introns begin with and end with Donor Splice Site Acceptor Splice Site D The average length of the 53 ORFs (Open Reading Frames) in Intron II is 15 codons. P D ( T ) T A cleaved from the β-Globin protein This negatively charged GU AG. Negative charge introduced into BPG binding site. Proline disrupts the alpha helix and eliminates a salt bridge to the alpha chain Promoter Region V C A YYYYYYYYYNCAG The longest ORF in this intron is 73 codons (62653-62871). AG GU G 2 results in unstable hemoglobin. soon after its synthesis. glutamic acid (E) is A G Reduced BPG binding results in increased O affinity. and eliminates the Bohr effect. replaced by a hydrophobic valine (V) in sickle cell anemia.

+ Sickle Cell Anemia The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β thalassemia). Hemoglobin Shepherds Bush Erythroid Specific Promoters β-Globin mRNA 0 Splicing Mutations Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β+ thalassemia). Hemoglobin Shanghai Hemoglobin Hiroshima Transcription continues No β-Globin protein is made due to non-functional donor splice site (β thalassemia). A Polyadenylation GT - Rich for 200 - 300 nucleotides. -75 CAAT Box -25 TATA Box begins here. EXON I + EXON II EXON III Polyadenylation Site T A A A Reduced level of β-Globin protein is made due to inefficient donor splice site (β thalassemia). A C G Signal Region A 3DMD Paper BioInformatics Activity© AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 62500 62540 62550 62600 62650 62700 62750 62800 62850 62900 62950 63000 63050 63100 63150 63200 63250 63300 63350 63400 63450 63500 63550 63561 63600 63650 63700 63750 © 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773 Map of the β-Globin Gene TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA Donor Splice Site Acceptor Splice Site Human β-Globin Gene on Chromosome 11 INTRON I INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II INTRON II Version 2.4 Version

Teacher Copy Teacher Copyright 2013 3D Molecular Designs, LLC 3 Forward a S Q C Q K S Q G Q V R L S S L R P H P V E P H P R V G Q S T P R S R E G R S Q G W A * K S G Q S H L L L T F A S D T T V F T S N L K Q T P W C T * L L R R S L P L L P C G A R * T W M K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q 40R F F E S F G D L S 50T P D A V M G N P K V60 K A H G K K V L G 70A F S D G L A H L D 80N L K G T F A T L S 90E L H C D K L H V D 100P E N F R V S L W D P * C F L S P S F L W L S S C H R K G R S N R V Q F R M G N R R M I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T * C L N I V Y N K R K Y L * D T L S N L K K N F T Q S A * Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T * S L Y I F M G * S V M F * Y V Y T Y * P N Q G N F A F V I L K N A F F F * Y T F L F I L F L I L S L I S F F Q G N N D T M Y H A S L H H S K E * Q * * F L G * G N S N I S A Y K Y F C I * I V T D V R G F I L L I A A T I Q L P F C F Y F M V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G * C P G P Q V S L S S L S C C P I S I K G S F V V Q L L N W G I L * R A L S I W I L P N K K H L F S L Q * C I * I I S E Y F T Globin Gene Map

- www.3dmoleculardesigns.com TM reading b A S A R R A K D R Y G C H H L D L T L W S H T L G L A N L L P G A G R A G A R A G H K S Q G R A I Y C L H L L L T Q L C S L A T S N R H H G A P D S * G E V C R Y C P V G Q G E R G * S W W * G P G Q V G I K V T R Q V * G D Q * K L G M W R Q R R L L G F * * A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L M L L W A T L R * R L M A R K C S V P L V M A W L T W T T S R A P L P H * V S C T V T S C T W I L R T S G * V Y G T L D V F F P L L F Y G * V H V I G R G E V T G Y S L E W E T D E * L H Q C G S L R I V L V S F I C C S * Q L F S F V * F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H * V T * K K T L H S L P S T L L F G I Y V C L F A Y S * S P Y F I F F Y F * L I H N H Y T Y L W V K V * C F N M C T H I D Q I R V I L H L * F * K M L S S F N I L F C L S Y F * Y F P * S L S F R A I M I Q C I M P L C T I L K N N S D N F W V K A I A I F L H I N I S A Y K L * L M * E V S Y C * * Q L Q S S Y H S A F I L W L G * G W I I L S P S * A L L L I M F I P L I F L P Q L L G N V 110L V C V L A H H F G 120K E F T P P V Q A A 130Y Q K V V A G V A N A L A H K Y H * A R F L A V Q F L L K V P L K S N Y * T G G Y Y E G P * A S G F C L I K N I Y F H C N D V F K L F L N I L L β ...where molecules become real frames 140 c P V P E E P R T G T A V I T * T S P C G A T P * G W P I Y S Q E Q G G Q E P G L G I K V R A E P S I A Y I C F * H N C V H * Q P Q T D T M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H * L S L P I G L F S H P * A A G G L P L D P E V L * V L W G S V H S * C C Y G Q P * G E G S W Q E S A R C L * * W P G S P G Q P Q G H L C H T E * A A L * Q A A R G S * E L Q G E S M G P L M F S F P F F S M V K F M S * E G E K * Q G T V * N G K Q T N D C I S V E V S G S F * F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L M P * H C V * Q K E I S L R Y I K * L K K K L Y T V C L V H Y Y L E Y M C A Y L H I H N L P T L F S F I F N * Y I I I I H I Y G L K C N V L I C V H I L T K S G * F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q * * Y N V S C L F A P F * R I T V I I S G L R Q * Q Y F C I * I F L H I N C N * C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F * V Q A R P F C * S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L M P W P T S I T K L A F L L S N F Y * R F L C S P T T K L G D I M K G L E H L D S A * * K T F I F I A M M Y L N Y F * I F Y * Consensus 1 2 3 4 5 6 7 8 9 10 20 30 Consensus Consensus Consensus A T EXON INTRON INTRON EXON Replacing histidine (H) with aspartic acid (D) CAAT Box GG C CAATCT TATA Box TATA ( ) A( ) The first methionine amino acid is Note: all introns begin with and end with Donor Splice Site Acceptor Splice Site D The average length of the 53 ORFs (Open Reading Frames) in Intron II is 15 codons. P D ( T ) T A cleaved from the β-Globin protein This negatively charged GU AG. Negative charge introduced into BPG binding site. Proline disrupts the alpha helix and eliminates a salt bridge to the alpha chain Promoter Region V C A YYYYYYYYYNCAG G The longest ORF in this intron is 73 codons (62653-62871). soon after its synthesis. glutamic acid (E) is AAG GU Reduced BPG binding results in increased O2 affinity. results in unstable hemoglobin. and eliminates the Bohr effect. replaced by a hydrophobic valine (V) in sickle cell anemia. G ...where molecules become real TM

Amino Acid Starter Kit©

“I can never again teach protein structure without toobers–they make it much easier for students to SEE !” Your students will explore the primary, secondary and tertiary structure of proteins © with this captivating kit. They will learn the chemical properties and atomic structure of the 20 amino acid side chains through the kit’s dual coloring scheme. Understanding protein structure begins with this unique combination of atomic and chemical properties. With the kit’s engaging, hands-on activities your students will gain a basic knowledge of protein folding before discovering the importance of secondary structure and active sites. Each 1-group set includes 1 chemical properties circle, 1 amino acid side chain chart, 22 amino acids, 1 4-foot mini toober, 15 plastic clips and 6 connectors.

! WARNING: CHOKING HAZARD Teacher notes, student handouts and interactive Jmol visualization tools are available

online at 3dmoleculardesigns.com/Teacher-Resources.htm. Starter Kit Acid Amino CAUTION: Science Education Product Project Lead the Way© selected the Amino Acid Starter Kit© for its BioMedical Sciences™ Program. 6-Group Set $314 (AASK-06) • 5-Group Set $263 (AASK-05) 3-Group Set $164 (AASK-03) • 1-Group Set $61 (AASK-01)

To increase your students’ understanding of proteins, see the ß-Globin Folding Kit© and Map of the Human ß-Globin Gene© (page 6), Insulin mRNA to Protein Kit© (page 9), Ribosome Mini Models (page 16), David Goodsell Cellular Landscapes (page 14), Amino Acid Starter Kit Poster© (below) and Genetic Codon Posters© (page 16).

Tertiary Structure Secondary Structure Active Site Amino Acid Side Chain Chart

Name Amino Acid Side Chain Name Amino Acid Side Chain Name Amino Acid Side Chain Name Amino Acid Side Chain

Alanine Glutamine Leucine Serine

© Ser Ala Gln Leu Amino Acid Starter Kit Poster A L S

Arginine Glutamic Lysine Threonine Acid Arg Lys Thr Glu K T © E

The Amino Acid Starter Kit Poster allows students to connect the chemical structure Asparagine Methionine Tryptophan

Asn Gly Met Trp © of each amino acid side chain as it is commonly represented in textbooks. The poster N G M W © Aspartic Histidine Phenylalanine Tyrosine features the same dual color scheme as the Amino Acid Starter Kit . Each atom of Acid His Phe Tyr Asp H F the side chain is color-coded according to atom type and each base is color-coded D

Cysteine Proline aline to reflect the overall chemical property of the side chain. Cys Ile Pro al C I P

Star Represents Negative Amino Acid Property Key Hydrophilic Side Chain Charge Carboxylic Atom Color Key Amino acid clip color and name color indicate property Cysteine Acid Group Clips attach to mini toobers in 3D Molecular Designs’ kits Threonine Amino O Kit Poster Group + - Methionine Glutamine © H3N C CO Aspartic Acid Positive Charge Hydrophobic H Alpha Carbon Carbon Oxygen Asparagine Leucine Proline Isoleucine Amino Acid Starter Kit Poster $24 (AASKP) ...where molecules become real TM 3eaeg O O O O + - Sulfur Glutamic Acid Tyrosine Histidine Serine H3N C C N C C N C C N C CO Lysine Arginine Tryptophan Phenylalanine Valine Glycine H H H H H H H © © Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2014, 2018 Version 4.0

Also see Amino Acid Starter Kit (above) and Genetic Codon Posters (page 16). Starter Acid Amino Zinc Finger Mini Model

A zinc finger is a short (~30 amino acid) protein motif that is often found in proteins that bind to DNA. Proteins with zinc fingers are one of the largest families of proteins found in the human genome. Each zinc finger consists of a two-stranded beta sheet and a short alpha helix. Its structure is stabilized by 2 cysteines and 2 histidines that bind to a single zinc atom. 3.5” Plaster Model $55 (ZFMM) © Zinc Finger Use this model with the Amino Acid Starter Kit (above), which asks students to build a toober Mini Model zinc finger model in the second protein folding activity. It can break if abused.

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

3dmoleculardesigns.com 7 ...where molecules become real TM

Spring 2019 Enzymes In Action Kit©

Enzymes In Action Kit Action In Enzymes Take your students beyond the simple lock-and-key concept of enzyme action with this dynamic, multifunctional kit. Color-coded foam pieces represent enzymes, a variety of substrates and inhibitors. Your students will use this kit to discover the specificity of substrate binding, how enzymes catalyze either catabolic or anabolic reactions and the effect of various inhibitors on enzyme action.

Each Enzymes In Action Kit© 1-group set contains 10 foam pieces (2 gray, 2 green, 2 orange, 1 red, 1 tan, 1 purple and 1 blue) and 1 sheet of stickers. Teacher notes and student handouts are available online at 3dmoleculardesigns.com/Teacher-Resources.htm. ! WARNING: CHOKING HAZARD

© CAUTION: Science Education Product 12-Group Set $121 (EAK-12) • 6-Group Set $62 (EAK-06) • 3-Group Set $35 (EAK-03) ! CALIFORNIA PROP 65 © WARNING: Also see Substrate Specificity Kit (below). Please see bottom of page 2 for details.

Substrate Specificity Kit©

Help your students achieve that “aha moment” with this simple but elegant kit that Substrate Kit Specificity demonstrates the highly-specific interaction between a substrate and an enzyme. With the Substrate Specificity Kit© students: • Use color-coded functional groups to construct a substrate and examine its chemical properties. • Use a mini toober to engineer an enzyme active site specific to the substrate constructed. • Explore different types of specificity including stereochemical specificity and absolute specificity. • Discover how subtle changes in enzyme structure can ! WARNING: CHOKING HAZARD potentially have a significant impact on substrate binding in the active site. ! WARNING: SMALL MAGNETS

© Lessons and activities are available online at CAUTION: Science Education Product 3dmoleculardesigns.com/Teacher-Resources.htm. ! WARNING: CALIFORNIA PROP 65 © Please see bottom of page 2 for details. Substrate Specificity Kit $41 (SSK-01) Also see Enzymes in Action Kit (above).

Acetylcholinesterase Active Site Cube©

Acetylcholinesterase Now your students can unfold an enzyme to see how the precisely

Active Site Cube positioned active site amino acids bind to specific substrates to catalyze a reaction. As your students open the active site cube they will see how the tightly-packed amino acid side chains bind the substrate (acetylcholine) and discover how 3 amino acids collaborate to cleave the neurotransmitter. Your students will explore how an insecticide targets the enzyme in mosquitoes and discover what happens when a mutation blocks the insecticide from binding to the enzyme, leading to the emergence of insecticide-resistant mosquitoes. His 480 Glu 367 © 5” Plaster Cube Model $950 (ACHASC-5) 3” Plaster Cube Model $499 (ACHASC-3) Ser 238 Acetylcholine Insecticide A mutant Not eligible for discounts (substrate) side chain

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

8 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM

Insulin mRNA to Protein Kit©

The Insulin mRNA to Protein Kit© helps your students understand that the specific sequence of amino acids in a protein is encoded by the specific sequence of nucleotides in the corresponding gene. After using the BioInformatics Map to search for the nucleotide sequence that encodes the amino acid sequence of insulin, your students will © fold a physical model of the 3-D structure of the insulin protein, using mini toobers (1 for the A-chain and 1 for the B-chain) and a folding map.

Each 1-group set includes student mRNA map, student folding map, 2 mini toobers, side chains, plastic clips, support posts, endcaps and an assortment of parts to mark and connect the chains. Teacher notes, student handouts and interactive Jmol visualization tools are available online at 3dmoleculardesigns.com/Teacher-Resources.htm.

6-Group Set $260 (INSFK-06) 3-Group Set $140 (INSFK-03) 1-Group Set $54 (INSFK-01) Insulin mRNA to Protein Kit Protein Insulin mRNA to It’s best if your students first use the Amino Acid Starter Kit© (page 7) before using the Insulin mRNA to Protein Kit©. Also see Insulin Model and Insulin Poster© (below), ß-Globin Folding Kit© (page 6) and Genetic Codon Posters© (page 16).

! WARNING: CHOKING HAZARD CAUTION: Science Education Product Please see bottom of page 2 for details. Insulin Model

The hormone insulin is an important regulatory protein that helps control blood sugar levels by signaling cells to take up glucose circulating in the blood. Our alpha carbon backbone model of insulin – now printed in more durable plastic – features a 51-amino acid with a longer B chain (orange) composed of an alpha helix and a beta strand, and a shorter A chain (purple) consisting of two alpha helices. The two chains are linked together by three disulfide bonds formed between the three pairs of cysteine side chains displayed in the model. Bring the basic principles of primary, secondary, tertiary and quaternary levels of protein structure to life in your classroom by exploring the structure of the insulin model.

5” Plastic Model $45 (INSPM) Insulin Model This model can be used as an accurate smaller scale template when using the Insulin mRNA to Protein Kit© (above). It can break if abused.

©

A Balancing Act Insulin Poster NUTRITION Glucose is the major fuel molecule that powers your cells. It • Glucose as Fuel • The Digestive System normally circulates in your bloodstream at a concentration of • The Endocrine System 90-110 mg/dL. Following a big meal, your blood glucose level can rise to 140 mg/dL or higher. This increase in glucose concentration triggers the release of the peptide hormone insulin from the pancreas into the bloodstream. Circulating insulin regulates the concentration of glucose in the blood INSULIN stream by (i) stimulating the liver to convert some of the glucose into glycogen, a storage form of glucose, and (ii) stimulating A U T other cells, like muscle, to take up glucose from the bloodstream. In both cases, the concentration of circulating glucose is decreased toward the normal level. L S By using the insulin protein as a starting point, teachers can weave together © C D DIABETES Controlling Diabetes People with Type I diabetes do not produce functional and BIOTECHNOLOGY insulin and therefore must control their blood glucose levels through glucose monitoring and insulin injections. a broad range of biology topics including the flow of genetic information, • Recombinant Insulin • Glucose continues to develop new technologies useful in Monitoring Devices • Insulin Pumps monitoring and managing glucose homeostasis. Current in-home tests consist of a main digital meter unit and disposable test strips that are inserted into the meter. These strips consist of multiple layers, electrodes, and chemicals such as glucose oxidase and potassium ferricyanide. When AC AC a drop of blood is placed on the strip, (i) the biochemistry and protein structure, cellular organelles, anatomy, physiology glucose in it reacts with the glucose oxidase to produce gluconic acid, (ii) which then reacts with the ferricyanide to form ferrocyanide, (iii) which is in oxidized by the electrodes, (iv) to generate an electric current that is directly proportional to the amount of glucose in the bloodstream. This current is then read and displayed by the meter. Combined with insulin pumps that release controlled amounts of insulin into the blood, this technology enables diabetics to maintain more control over their and cell biology of glucose homeostasis, energy metabolism, the endocrine and blood glucose levels. BIOCHEMISTRY • Protein Structure • Membrane Receptor Proteins • Signal Transduction C LEU PRO PRO GLN digestive systems, recombinant DNA technologies and new approaches to monitor ALA GLY VAL GLY GLY LEU GLN GLY GLU VAL GLU ALA GLN LEU LEU LEU ASP SER GLY GLY GLY GLU SER Cleavage Site SS ALA MOLECULAR LEU C-terminus GLU Cleavage GLN ARG Site LYS BIOLOGY ARG GLY ILE VAL GLU GLN CYS CYS THR SER ILE CYS SER LEU GLU ASN TYR CYS ASN ARG THR SS • Gene Structure • Transcription CELL BIOLOGY LYS PRO Preproinsulin > blood glucose levels and control diabetes. PHE TYR THR • Protein Synthesis VAL GLU ALA TYR LEU VAL CYS GLY GLU ARG GLY PHE Proinsulin > Insulin RECOMBINANT • Glucose Transporters • Membrane Tracking LEU HIS Active insulin is a 51 amino acid peptide hormone, SS SER made up of a B-chain (20 amino acids) and an A-chain GLY INSULIN GLY CYS LEU HIS GLN ASN VAL PHE (31 amino acids). It is initially synthesized as one long, N-terminus continuous protein composed of a pre- or signal sequence (24 amino acids), the B-chain (31 amino acids), the C-peptide (35 amino acids) and the A-chain (20 amino acids). Following its synthesis by a ribosome, preproinsulin in cut up by a series of proteases to generate the © Insulin Poster nal, active form of the hormone. A protease rst clips the pre-signal from the Insulin N-terminal end of the protein. The remaining protein folds up into a compact structure that Gene is stabilized by the formation of covalent disul de bonds. Subsequent clipping in two places by proteases found in the Golgi releases the C-peptide from the functional insulin protein. Insulin Poster $21 (INSP) When released into the bloodstream, insulin binds to speci c insulin receptor proteins Also see Insulin mRNA to Protein Kit (above). found in the membranes of muscle cells and fat cells and stimulates the uptake of glucose by these cells (see Cell Biology). Expression Vector

Split Ge . . . nes The human insulin gene is located on chromosome 11. Like other eukaryotic genes, it is split up into exons (3) and introns (2). When RNA polymerase Insulin receptors — and GLUTs transcribes the insulin gene, it initially makes a 1,858 Insulin stimulates the uptake of glucose from the blood stream by muscle and nucleotide long precursor mRNA. As this precursor New Approaches for Treating Diabetes fat cells in a surprisingly indirect way — by increasing the number of glucose mRNA is transported out of the nucleus, the two transporter proteins (GLUTs) present in the membranes of these cells. When insulin introns are spliced out to generate the 353 nucleo- From 1922 to the 1980’s, the insulin used by diabetic patients was puri ed from binds to its speci c receptor protein in the membrane of a cell, it triggers the tide long mature mRNA. As this insulin mRNA is cows or pigs. While these were not identical to the human form of the hormone, bound by a ribosome and translated into protein, they eectively regulated glucose levels in human patients. With the advent of phosphorylation of a series of proteins — that in turn phosphorylate other proteins. The net result of this “signal transduction cascade” is the movement of storage vesicles, the pre-signal – the rst 24 amino acids of the recombinant DNA technologies, it became possible to synthesize human insulin in TM protein – directs the ribosome to the endoplasmic bacteria. In 1978, Genentech and City of Hope National Medical Center scientists whose membranes are saturated with GLUTs, to the cell surface where they fuse with ...where molecules become real reticulum. Preproinsulin is then extruded into the the cell membrane. The resulting increase in the number of GLUTs in the cell’s mem- produced human insulin using recombinant DNA technology. This was done by 3eaeg lumen of the endoplasmic reticulum as it is being chemically synthesizing genes for the two chains of insulin and inserting them into brane then allows glucose to enter the cell. As glucose levels in the blood fall, insulin synthesized. It is then processed into the nal, levels fall, and GLUTs are removed from the cell membrane by endocytosis and returned to active form of the hormone by a series of proteo- E-coli. The process was licensed to Eli-Lilly to develop and re ne. By 1980, clinical studies lytic cleavages. For a stunning illustration of this for the new drug had begun, and as of 1982, Eli-Lilly’s Humulin became the rst genetical- their intracellular storage compartment. To see an animation of this process, visit ow of genetic information see David Goodsell’s ly engineered drug approved by the FDA. For a detailed history of recombinant insulin http://cbm.msoe.edu/teachRes/animations.html. Machinery of Life (Springer, 2009; page 73). see Stephen Hall’s Invisible Frontiers: the Race to Synthesize a Human Gene (Oxford, 1987). Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2014, 2018 Version 1.3

3dmoleculardesigns.com 9 ...where molecules become real TM

Spring 2019 CRISPR/Cas9 Models

Give your students a hands-on exploration of the next generation in genetic engineering! We are thrilled to be able to offer an affordable version of the 3D-printed Cas9 component of the CRISPR gene editing CRISPR/Cas9 Models technology. Jennifer Doudna, PhD, Professor at UC-Berkeley and Executive Director of the Innovative Genomics Initiative (IGI), is one of the pioneers of the CRISPR/Cas9 technique, which allows researchers to make specific changes to the genetic code of cells and organisms. 3D Molecular Designs designed and built the model for Dr. Doudna with Jacob Corn, PhD, Scientific Director of the IGI. The front segment detaches from the model, allowing students a closer look at the guide RNA and two strands of DNA inside. ! WARNING: CHOKING HAZARD 5” Nylon Model $498 (NCC9M-5) ! WARNING: SMALL MAGNETS 11” Nylon Model $1,450 (NCC9M-11) 5” Plaster Model $246 (CC9MM-5) CAUTION: Science Education Product Not eligible for discounts ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details.

Hemoglobin Nylon Model

If you could have only one model with which to teach proteins, this is it — a Nylon Model Hemoglobin durable, hand-painted nylon model of hemoglobin! This quaternary complex α includes 2 -chains and 2 ß-chains. One of the ß-chains is magnet-docked so it can be removed for closer examination. The heme group and its oxygen on the removable ß-globin are also magnet-docked. The glutamic acid side chain at position 6 of the ß-globin chain can be exchanged for a valine side chain — representing the change in the ß-globin protein that leads to sickle cell anemia. 6.5” Hemoglobin $750 (NHGM) Not eligible for discounts

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

Hemoglobin PosterHemoglobin© Poster©

The Oxygen Transporter

W D W S C A We all know that we must breathe to stay alive. ut what does An Inherited Disease Hemoglobin Hemoglobin this really mean We need oygen to burn the fuel food that From exploring the question, “Why do we breathe?” to illustrating the structure A mutation in the β-globin gene is we eat to release the energy that powers our bodies. Every responsible for the genetic disease H P S time we take a deep breath, our respiratory system and our sickle cell anemia. When the circulatory system collaborate to deliver oygen from our lungs emoglobin is a protein nucleotide at position 2 in the to all of the tissues of our body. s our heart pumps red blood composed of four subunits two gene is changed from to T, the cells through our lungs, they pick up by binding it to a αglobin subunits and two 2 codon changes from to , of hemoglobin, the cause of sickle cell anemia and the physiology of oxygen special protein called hemoglobin. Each red blood cell contains Glutamic Acid Valine β-globin subunits. Only proteins Poster and th amino acid of the protein is with muiltiple subunits ehibit approimately 2 million copies of this hemoglobin protein. changed from glutamic acid lu to valine al. uaternary structure. Each emoglobin is able to bind and prevent it from reacting © 2 The normal amino acid, lu, is negatively protein subunit has a tightly inappropriately with other molecules while it is being delivered I charged and is eposed on the outside surface of bound , which in to distant parts of our body. turn binds one molecule to the protein, where it interacts with water and transport, our colorful Hemoglobin Poster will spark new inquiry among your 2 an iron atom in the center of the contributes to the solubility of the protein inside heme group. It is this heme group Heme Group β Subunit red blood cells. When changed to al a that gives blood its red color. lutamic cid hydrophobic amino acid the solubility of the The β-globin protein is composed of 6 amino lutamic cid ocation of mutant protein is reduced, and the hemoglobin Sickle Cell utation acids. This protein spontaneously folds up into ocation of proteins begin to stick together. This aggregation students. Best used as a companion guide for 3DMD’s Hemoglobin Nylon Sickle Cell of the mutant protein distorts the shape of the red its compact globular shape, following basic principles of chemistry and physics utation blood cells. These sickled cells clog up the very © © narrow blood vessels in capillary beds, leading to The hydrophobic amino acids are buried on α Subunit the complications of sickle cell anemia. the inside of the protein, where they are protected from water. Model (above), ß-Globin Folding Kit , Map of the Human ß-Globin Gene and The polar and charged amino acids are

© positioned on the surface of the protein, where they interact with water. Positivelycharged basic amino acids often interact with negativelycharged acidic amino ß-Globin Mini Models (page 6), the poster can also stand alone to help facilitate acids to further stabilize the folded structure.

meaningful discussions about hemoglobin. α Subunit Normal Red Blood Cells Sickled Red Blood Cells H G eme roup β Subunit If each β-globin protein consists of a uniue © seuence of 6 amino acids, how does the cell remember the correct seuence of amino Hemoglobin α β acids to oin together to make this protein 2 2 2 T P O T Hemoglobin Poster (21” x 22”) $21 (HGP) million times in each red blood cell The The structure of hemoglobin has evolved over time to result answer is . The seuence of amino acids Lungs in a protein that is euisitely suited to transport oygen. The in the β-globin protein is encoded in the pH = 7.4 seuence of nucleotides that make up the foursubunit hemoglobin is designed to efficiently bind 2 in

βglobin gene. ecause cannot leave the Tissue the oygenrich environment of the lungs P 8 torr and 2 , pH = 7.2 nucleus and move to the cytoplasm where then efficiently release this 2 in the oygenpoor ribosomes are ready to make protein, the environment of peripheral tissues P 26 torr. oreover, 2

gene is first copied into messenger . The of Hemoglobin Saturation Percent the more acidic environment of actively eercising muscle seuence of nucleotides in the messenger triggers oygen release for use in generating energy. PO (torr) is CCCCCC... 2 In the cytoplasm, ribosomes then translate this There are separate genes for αglobin and There are several different versions of the β-globin gene, messenger threenucleotidesatatime βglobin proteins. In developing red blood cells, Oxygen Affinity used at different developmental stages, to produce versions triplet genetic codon into the correct seuence the epression of the globin genes is regulated When you eercise vigorously, your muscles become deprived of . They switched from aerobic respiration of amino acids that make up the β-globin so that equal numbers of αglobin and βglobin 2 of the hemoglobin protein that will most efficiently deliver 2 to fermentation, producing lactic acid. This lowers the protein etaliseuThrProlu.... The proteins are made, to allow the efficient p of the muscles. t a lower p, hemoglobin releases to the developing fetus. Fetal hemoglobin binds oygen more

initial methionine is later removed. assembly of the foursubunit hemoglobin. 2 more easily, providing the 2 that the muscles need. readily than adult maternal hemoglobin.

To view an online mol tutorial showing how basic principles of chemistry drive the folding of the β-globin protein, visit 3dmoleculardesigns.com/Teacheresources/minocidStarterit.htm

...where molecules become real TM

3eaeg

Copyright 3 olecular esigns ll ights eserved 2, 2, 28 ersion 3.

10 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM

NEW Dynamic DNA Kit©

“I can use it with multiple levels to reveal higher knowledge concepts.” Introducing our new Dynamic DNA Kit© - a next generation teaching tool that will help your students better understand how the genetic information in DNA is revealed and used. Dynamic DNA includes the best features of our popular DNA Discovery Kit©: It’s accurate © and easy to put together. Students can assemble the nucleotides, feel the hydrogen bonding of the A-T and G-C base pairs and discover the double helical structure of DNA. But now – thanks to patented design innovations – they can also twist and unwind the double helix to model DNA replication and RNA transcription!

Field-tested by teachers, the 12 Base Pair Set includes 6 A-T and 6 G-C base pairs, 5’ hydrogen and 3’ oxygen parts, oxygen atoms to model RNA, removable carbons for uracil, ATP, TTP, GTP and CTP models and display stand. Dynamic DNA Kit Lessons and activities are available online at 3dmoleculardesigns.com/Teacher-Resources.htm. 12 Base Pairs (Classroom Set) $237 (DDNA-12) • 6 Base Pairs $124 (DDNA-06) “This will hook a kid!” 2 Base Pairs $45 (DDNA-02) • 6 Sets of 12 Base Pairs $1,249 (6DDNA12)

Hemoglobin Nylon Model Experience the dynamic flexibility of DNA with a better kit at a lower price! Assemble the nucleotide’s nitrogen base, sugar and phosphate group.

“This is literally the diagram 6.5” Hemoglobin $750 (NHGM) Not eligible for discounts from the textbook that students can manipulate!” DNA replication

5’ to 3’ synthesis

Major groove

Adenosine triphosphate Minor groove

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROP 65 Thymine to uracil conversion for Please see bottom of page 2 for details. RNA transcription 3dmoleculardesigns.com 11 ...where molecules become real TM

Spring 2019 Molecules of Life Collection©

© The Molecules of Life Collection features plaster models of the 4 major types Magnified 20 Million Times NUCLEIC ACIDS Nucleic acids such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are composed of monomers known as nucleotides. DNA is a long, linear polymer of four dierent nucleotides — adenine, thymine, guanine and cytosine (A,T,G,C). The sequence of these four nucleotides in your DNA species the sequence of amino acids in your proteins. Two strands of DNA wrap around each other to form a right-handed double helix. This double helix contains of biomolecules — nucleic acids, proteins, lipids and carbohydrates. Since the complementary A-T and G-C base pairs. In 2001, researchers determined the exact nucleotide sequence of the 3.2 billion base pairs of the human genome. COMPLEX CARBOHYDRATES PROTEINS Complex carbohydrates (polysaccharides) consist of many Your body produces monosaccharide (simple sugar) molecules joined together. approximately 100,000 Plants use glucose monomers to build two dierent linear biomolecules exist and interact in an aqueous environment, water is also included. dierent proteins, each polymers: either starch or cellulose. You, as a human being, have with a specic shape an enzyme (protein) that cuts o the individual glucose monomers that allows it to of starch – but not cellulose – so that glucose can be oxidized to release its energy. When you eat a meal, some of the glucose is stored perform a specic DNA function. Aquaporins in a branched polysaccharide called glycogen. Glycogen rapidly releases are channel proteins glucose to provide energy. Two single building block models go with each biomolecule. A major teaching point that facilitate the selective diusion of water in single le across a cell membrane. Thirteen variants of aquaporin have been identied in Glycogen is that large complex biomolecules are made of small, simple building block units. humans. Each is composed of 250-300 NUCLEOTIDES amino acids. Two polar Nucleotides are the building blocks of your DNA and RNA. There are four nucleotides in asparagine amino acids DNA, each composed of a base — adenine (A), thymine (T), guanine (G) or cytosine (C) — a located near the center deoxyribose sugar, and a phosphate group. In RNA, the deoxyribose is replaced by ribose, and the of the channel guide thymine base is replaced by uracil. In both DNA and RNA, enzymes called polymerases join the monomer All models are built to the same scale — 20 million times their real size. the water molecules nucleotides together to make long polymers. Cells use the unique sequence of nucleotides in DNA as a code rapidly through Aquaporin to build the correct sequence of amino acids in a protein. the membrane. To see water molecules passing through the channel, MONOSACCHARIDES HO nd the green monomer and gently separate its section Monosaccharides (simple sugars) are Cellulose from the rest of the model. energy-rich molecules that provide fuel The pink oxygen highlights where water molecules ip for your body. Glucose is a monosaccharide that plants build from over in the protein. AMINO ACIDS carbon dioxide and energy from the sun, in a process called Starch Amino acids are the monomer building blocks of photosynthesis. The energy stored in glucose is released when The purple dot highlights the sixth carbon in each glucose. proteins. There are 20 amino acids — each with a organisms break down food during cellular respiration. This dierent shape and chemical property. As they energy is captured as ATP and used to power life processes.

Molecules of LifeMolecules Collection join together in a distinct sequence — specied The entire set includes 17 models: DNA, adenosine monophosphate, aquaporin, by your DNA — they spontaneously fold into a PHOSPHOLIPIDS compact shape following basic principles of ICE STRUCTURES Phospholipids are unusual chemistry and physics. molecules with two distinct Water can exist in any one of three states — gas (vapor), properties. One portion of the liquid or solid (ice). At 0o Celsius (32o Fahrenheit) the molecule is a long water-avoiding thermal motion of the water molecules slows to the WATER MOLECULES (hydrophobic) carbon tail. The point that stable hydrogen bonds form between the Life happens in water. The human body is about other portion is a water-seeking molecules and an ice lattice forms. Ice oats since ice 70% water. This unique polar solvent provides CELL MEMBRANES asparagine, cell membrane, phospholipid, starch, glycogen, cellulose, glucose, ice (hydrophilic) phosphate group. lattices are less dense than liquid water. This causes lakes to the medium in which the macromolecules of Phospholipid bilayers form In your cells, phospholipid freeze from the top down, insulating the life beneath. Water your cells oat. Biomolecules interact with cell membranes to separate molecules spontaneously molecules can form more than a dozen crystalline structures each other in your cells following basic the inside of your cells from the assemble into a lipid bilayer depending on temperature and pressure; however, nearly all ice principles of chemistry and physics. outside. The hydrophobic nature with the hydrophobic carbon on the Earth's surface and in its atmosphere is a hexagonal phase of a phospholipid bilayer prevents tails buried and hidden from denoted as ice Ih. the free movement of most small polar water molecules in the cell. structure and water molecule. molecules into and out of your cells. The polar phosphate portion of Proteins embedded in cell membranes phospholipids is on the allow ions and small molecules to pass Water surface, exposed to water. through the membrane. Each protein has a specic shape that allows it to pass a specic molecule — such as water — into or out of the cell.

B Lipid Bilayer UILDING BLOCKS The models sit on a 24’’ x 22’’ placemat that includes a description of each Hexagonal Ice (Ih) Introduction Exploration Four classes of biomolecules – proteins, nucleic acids, carbohydrates and lipids – are Use the Molecules of Life Placemat and the accompanying models to explore the Color Key found in living cells. Proteins, nucleic acids and carbohydrates are macromolecules following concepts: comprised of a small number of monomeric subunits: amino acids, nucleotides and Each of the structures featured is essential to sustain life. Indicates one building block unit within each monosaccharides, respectively. Since they interact in an aqueous environment, we Large biological polymers — DNA, proteins and complex carboyhdrates — are structure have included water in the Molecules of Life Collection©. Lipids are a diverse group composed of smaller building block monomers — nucleotides, amino acids and Phosphorous Carbon of molecules that interact with each other through “hydrophobic interactions” monosaccharides. structure. Individual 8.5’’ x 11’’ workstation mats, teacher notes and student rather than covalent bonds, and generally are not large enough to be considered Aquaporins and other proteins embed in the cell membrane to allow water and macromolecules. other molecules or ions to pass in and out of the cell. Hold the aquaporin and cell Oxygen Nitrogen

TM membrane models next to each other, as you discuss water transport through the ...where molecules become real Remember that these structures are dynamic and exible, not rigid like the plaster cell membrane. Sulfur Hydrogen* models included in the Molecules of Life Collection©. 3dmoleculardesigns.com All biomolecule and building block models are shown at the same scale. They are To increase your understanding of the concepts related to the Molecules of Life magnied 20 million times. *Not all hydrogens are shown on these images. featured above, you may also want to use 3D Molecular Designs’ Water Kit©, DNA The size of an atom is the same in all molecules in which it is present. For example, Discovery Kit©, Flow of Genetic Information Kit©, Amino Acid Starter Kit©, and oxygen, shown in red, is the same size whether it is in a nucleotide, amino acid, handouts are available online to download and print at © sugar, phospholipid or water. Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 5.1 Phospholipid & Membrane Transport Kit . 3dmoleculardesigns.com/Teacher-Resources.htm.

Molecules of Life Collection© (17 plaster models and placemat) $650 (MLC) Molecules of Life Collection© Not eligible for discounts Molecules of Life Monomer Set© (2 models of each monomer) $72 (MLC-AM) DNA (2 monomers and 1 polymer) $242 (MLC-D)

© Carbohydrate (2 monomers and 3 polymers) $136 (MLC-S) Lipid (2 phospholipids and 1 lipid bilayer) $379 (MLC-L) Protein (2 monomers and 1 polymer) $269 (MLC-A) Ice (2 monomers and 1 polymer) $34 (MLC-I) Molecules of Life Placemat© (without models) $21 (MLC-PM) Protein Adenosine Triphosphate $16 (MLC-ATP) This model is built to the same scale but is not part of the Molecules of Life Collection©. It must be purchased separately.

Ice

The aquaporin model Hold the aquaporin and lipid models opens to show water next to each other as you discuss how molecules rolling proteins embed in cell membranes to Glycogen over in their passage allow water and other molecules or through the channel. ions to pass in and out of the cell. Cellulose

Lipid

Starch Carbohydrate

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details. Adenosine Triphosphate DNA Molecules of Life Monomer Set

12 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM

Flow of Genetic Information Kit©

Don’t be surprised if one of your students blurts “Now I get it!” while using our Flow of Genetic Information Kit©! Manipulating the kit’s color- coded foam nucleotides and placemats, students: • Model replication of the leading and lagging strands of DNA. • Model transcription as they copy one strand of DNA into mRNA using an RNA polymerase.

• Model translation/protein synthesis as they decode the © mRNA into protein on the ribosome placemat. Your students can then explore the folding of the protein into its final 3D shape using our popular Amino Acid Starter Kit© (page 7).

Lessons and activities are available online at 3dmoleculardesigns.com/Teacher-Resources.htm. Flow of GeneticKit Information 1-Group Set $114 (FGIK-01) 3-Group Set $308 (FGIK-03) 6-Group Set $552 (FGIK-06) Additional DNA & RNA Nucleotide Set $23 (FGIK-ANS) ! WARNING: CHOKING HAZARD Side Chain Expansion Pack $27 (FGIK-SCEP) tRNA Expansion Pack $19 (FGIK-TEP) CAUTION: Science Education Product © © © ! WARNING: CALIFORNIA PROP 65 Also see Dynamic DNA Kit (page 11), DNA Starter Kit (page 20) Molecules of Life (page 12) Please see bottom of page 2 for details. and Tour of a Human Cell© (page 14).

Demo DNA Nucleotides© © Using these large-scale, color-coded foam nucleotides, you can teach the complementary A-T and C-G base pairs and the antiparallel nature of double-stranded DNA. Move on to the flow of genetic information as you teach the basic processes of semiconservative DNA replication and mRNA transcription. You can then stretch your students by introducing PCR (polymerase chain reaction) and the Sanger DNA sequencing method — and much more. One set contains 80 nucleotides: 20 As, 20 Ts, 20 Cs and 20 Gs. Demo DNA Nucleotides© $43 (DDNS-01) Also see Dynamic DNA Kit© (page 11), DNA Starter Kit© (page 20), Molecules of Life© (page 12) and Tour of a Human Cell© (page 14).

! WARNING: CHOKING HAZARD Demo DNA Nucleotides CAUTION: Science Education Product Please see bottom of page 2 for details.

3dmoleculardesigns.com 13 Tour of a Human Cell I

This illustration simulates what we would see if we could TM K magnify a portion of a living cell ...where molecules become real by 1,500,000 times. At this H G magnication, atoms would be B about the size of a grain of salt, H cells would be the size of huge buildings, and you would be roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules in the cell are shown, including Spring 2019 A proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A David Goodsell Cellular Landscapes D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to David Goodsell, PhD, scientist, author and artist of all things small, creates cellular landscapes that accurately illustrate the size, processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C shape and distribution of proteins in their natural environment of the cell. These unique images connect the molecular world, C B inferred by X-ray crystallography and NMR spectroscopy, with the cellular world, observed by light and electron microscopy. C D G E G B These laminated prints of Goodsell’s stunning water color paintings illustrate biology in a dimension not seen in other The Machinery of Life E F instructional tools. Adjacent text identifies the structures and explains their functions. Whether teaching the flow of genetic F This image is taken from The Machinery of Life by David S. J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be information, the many jobs of proteins, energy metabolism or the immunology of a flu shot, these landscapes may be the used to explore the ultrastructure of cells, and X-ray B crystallography and NMR spectroscopy may be used to missing piece in your current collection of instructional tools. reveal the atomic structure of individual puried molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com © Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics. Tour of a Human Cell

Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signalTour recognition of a Human particle (B)Cell and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesiclesI to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). delivered to the endoplasmic reticulum surface. Later, the signal sequenceThis illustration simulates what is clipped proteins are transported to the next step in small transport vesicles, formed by a cell in small transport vesicles. The protein clathrin (C) provides the molecular with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of we would see if we could The Golgi is the processing and sorting plant of the cell. Sugars and lipids are K The cytoplasm of our cells is lled with enzymes and other proteins performing their magnify a portion of a living cell o when the protein is fully synthesized and safely delivered inside.by 1,500,000 Inside, times. At this a coat of COPII proteins (I). Any defective proteins are transported out of the H attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments that do not encode proteins. Once the RNA is properly edited, it is delivered out G many tasks. These include ribosomes (D) and the other machinery of protein synthesis, read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled magnication, atoms would be B about the size of a grain of salt, H collection of chaperonins such as BiP (C), Grp94 (D), calnexin and proteincells would be the size ofdisulde huge endoplasmic reticulum and destroyed by the proteasome (J). the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as buildings, and you would be enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with ...where molecules become real roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A cbm.msoe.edu 3dmoleculardesigns.com proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016 Version 1.1 - 2/2016 D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C C B C D G E G B The Machinery of Life E F F This image is taken from The Machinery of Life by David S. J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be used to explore the ultrastructure of cells, and X-ray B crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics.

Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments ...where molecules become real TM I with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. www.3dmoleculardesigns.com Tour of a Human Cell Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018

This illustration simulates what we would see if we could K I magnify a portion of a living cell Tour of a Human Cell Tour of a Human Cell This illustration simulates what K by 1,500,000 times. At this we would see if we could H magnify a portion of a living cell by 1,500,000 times. At this H G G magnication, atoms would be magnication, atoms would be “The complexity of a cell is so very visible!” B about the size of a grain of salt, H B cells would be the size of huge about the size of a grain of salt, buildings, and you would be roughly one-fourth the size of the H earth in height, allowing you to J H cells would be the size of huge walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A buildings, and you would be proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D roughly one-fourth the size of the omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, “SoA many topics can be addressed using the grand panorama – I can’t earth in height, allowing you to and many other small molecules. H J D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G walk across the continent in a few the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C steps. All of the macromolecules C B C D in the cell are shown, including G A E imagine teaching cell biology without it!” proteins, nucleic acids, carbohy- G B B A The Machinery of Life E I F F This image is taken from The Machinery of Life by David S. drates and lipid bilayers, but all of J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be the smaller molecules have been used to explore the ultrastructure of cells, and X-ray B © crystallography and NMR spectroscopy may be used to A D reveal the atomic structure of individual puried omitted for clarity. In reality, the molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E The Tour of a Human Cell Panorama will take your students from the nucleus to empty spaces in this picture are experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics. lled with water, ions, sugars, ATP, A Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered and many other small molecules. DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, thesuch as the antibodies made by thisouter plasma cell, the journey starts with the ribosome,cell and it is quickly recognized by amembrane. signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H).In Finally, the new theproteins nucleus, like giantin (A) and GM130 (B) guide the vesicles to the right place. DNAthe proteins are properly modied and sorted, theyis are delivered throughoutwrapped the clathrin coat falls o and the vesicle is guided to its ultimate destination.around(B). Long tethering proteinshistones like golgin (C) help the vesicle nd its proper destination. intermediate forming laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments D TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated www.3dmoleculardesigns.com nucleosomes. RNA polymerase unwraps the DNA and makes mRNA which is deliveredCopyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to processing in the Golgi, and nishing with transport and secretion at the cell surface. through nuclear pore complexes to ribosomes where antibody proteins are made and C J C C delivered into the endoplasmic reticulum. Vesicles carry the protein through the Golgi B C D G and kinesin motor proteins pull the antibodies to the cell membrane — a wonderful

E © G B example of the immunology of your flu shot. The Machinery of Life E F F This image is taken from The Machinery of Life by David S. Teacher resources including a student activity sheet are available with purchase of J Goodsell. It reveals a previously unseen level of F A biological scale. Light and electron microscopy may be the panorama. used to explore the ultrastructure of cells, and X-ray B crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried With our new combo you can give your students a more intimate and interactive experience as you lead them molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E in an exploration of the complexity of cell structure and function. You’ll find yourself referring back to the experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics. landscape multiple times throughout the school year! The combo includes 1 Grand Panorama (approx. 11 feet long) and 6 Panoramas (approx. 6 feet long). Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded© sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteinsTour by oligosaccharyl of transferasea Human (H). Finally, the new Cell Grand Panoramaproteins like giantin (A) and GM130 23” (B) guide x the 11’ vesicles to$95 the right place. (DGTHC-GP)the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi© is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum Tourand destroyed byof the proteasomea Human (J). Cell Panorama 11” x 70” $59 (DGTHC-P) enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real TM cbm.msoe.edu 3dmoleculardesigns.com 1-Grand Panorama and 6-Panoramas Combo $415 (DGTHC-01GP-06P)

Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016 Version 1.1 - 2/2016

A N S

Acetylcholine Signaling A synapse is a junction where a nerve cell (neuron) communicates with another cell across a narrow gap via a neurotransmitter or an electrical coupling. One speci c kind of synapse is a neuromuscular junction, where chemical signals are transmitted from the neuron to a muscle cell across the synapse, shown here in cross-section. The end of the axon is shown at the top, with two vesicles full of neurotransmitters inside the axon terminal. The vesicle on the left is docking to the membrane. The vesicle on the right has fused with the membrane and is releasing the Neuromuscular Synapse Poster neurotransmitter acetylcholine. A complex collection of tethering and regulatory proteins in the vesicle membrane is needed to perform this delicate task, and voltage-gated calcium channels (A) in the neve membrane help decide when to begin. The synapse between the cells is lled with basement membrane, which Neuromuscular Neuromuscular

Synapse Poster also includes the enzyme acetylcholinesterase (B), which breaks down acetycholine into choline and acetate after it is nished with its job. The small protein CHT1 (C) transports choline © back into the cell to be recycled for the next nerve impulse. A muscle cell is shown at the bottom, with many acetylcholine receptors (D) on its surface. A tangled The Neuromuscular Synapse Poster (right) illustrates the molecular interactions found at network of proteins inside the muscle cell holds the receptors in place, clustering them within the synapse (3,000,000X).

O CH N CH HC O CH A

H O a neuromuscular synapse — where vesicles filled with the neurotransmitter, acetylcholine, A

O CH N CH HC O HO CH are fusing with the membrane of the pre-synaptic neuron. Following vesicle fusion, the A C The Machinery of Life This image is taken from The Machinery of Life by David S. Goodsell. It reveals a previously unseen level of biological scale. Light and electron microscopy may be used to explore the ultrastructure of cells, and X-ray crystallography and NMR spectroscopy may acetylcholine diffuses across the synaptic space to bind to acetylcholine receptors found in be used to reveal the atomic structure of individual puri ed molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. Instead, this illustration is synthesized by combining experimental data on cellular ultrastructure, the atomic structure of the membrane of the muscle cell. Acetylcholinesterase is entangled in the synaptic space, molecules, and bioinformatics. where it breaks down the neurotransmitter, ending neuronal signaling.

© This book is available from Neuromuscular Synapse Poster 23” x 30” $29 (DGNSP) major booksellers.

Also see the Dynamic DNA Kit© (page 11) and DNA Starter Kit© (page 20) and the following mini

...where molecules become real TM models: Nucleosome, Ribosomes and tRNA (page 16), Antibody, Hemagglutinin and Influenza Virus 3dmoleculardesigns.com Copyright 3D Molecular Designs All Rights Reserved - 2009, 2016, 2018 Capsule (page 17). Version 2.1 Neuromuscular Synapse Poster©

14 Flu Fight: Immunity & Infection In uenza Virus Infection Cycle Panel 2 (below) - Docking and Receptor-Mediated Endocytosis of the In uenza Virus. In Panel 3 (top right) - pH-Induced Conformational Change in the Structure of the HA Protein. vATPases (V), located in the the absence of neutralizing antibodies, the neuraminidase (N) on the surface of the virus membrane of the endosome, pump protons into the endosome, which lowers the pH from ~pH 7 to ~pH 5. This drop in pH triggers a V digests some of the carbohydrate chains on the mucin proteins, allowing the virus to penetrate conformational change in the structure of the HA proteins within in the viral membrane (VM), exposing the fusion of the EM deeper into the mucosal barrier and ultimately to the surface of ciliated epithelial cells. If IgA trimeric HA protein, which then embed themselves in the endosomal membrane (EM). Antibodies in Action antibodies have not neutralized the hemagglutinin (HA) protein on the surface of the virus, it binds to sialic acid receptor...where proteins (R) molecules embedded in the become surface of the real epithelial TM cell. This Panel 4 (bottom right) - Membrane Fusion and Release of Viral RNA into the Cell. After the fusion peptides of the HA proteins Panel 1 - Antibodies in Action. The mucosal barrier that lines the ciliated epithelial cells of the upper respiratory tract in humans is composed of a thick network of triggers receptor-mediated-endocytosis wherein clathrin (C) and AP-2 (AP) proteins are embedded in the endosomal membrane, further conformational changes in the structure of HA brings the viral membrane closer proteins that works to trap and neutralize the virus, and to activate additional antiviral responses. Mucins (M) and IgA antibodies (A) are two kinds of proteins found in the spontaneously assemble into a geodesic dome-like structure and engulf the virus within a to the endosomal membrane. At the same time, protons ow into the virus through the M2 proton channel protein (M2), weakening HA mucosal barrier that limit access of the virus to the cell surface. Mucins are long, brous proteins that intertwine to create a thick, viscous network that nonspecically cellular membrane – creating an endosome. Other components of the in uenza virus include, the interaction between the matrix proteins (M1) and the viral RNA genome. As the viral membrane fuses with the endosomal traps particulate matter and pathogens. IgA antibodies are produced in our adaptive immune system in response to either a vaccine or a previous infection. They bind M1 matrix protein (M1), M2 proton channel protein (M2), RNA polymerase (RP) and the membrane, the segmented viral RNA genome is released into the cytoplasm of the cell. This completes the rst stage of the VM primarily to regions of the hemagglutinin (HA) protein found on the surface of the in uenza virus, which blocks hemagglutinin from binding to the sialic acid receptor segmented RNA genome. in uenza virus infection cycle. proteins (R) on the surface of epithelial cells – the rst step in the in uenza virus infection process (Panel 2). The secretory component (SC) shown bound to dimeric IgA antibodies represents a protein involved in the transport of IgA proteins from the basal membrane of the epithelial cells to the apical membrane where it is secreted into the mucosal barrier. Other proteins such as interferon (I) and lactoferrin (L) make up part of the innate immune system that activates other nonspecic antiviral defense mechanisms. When viruses aren’t neutralized by antibodies, they attach to cells and begin endocytosis (Panels 2, 3 and 4). Flu Fight: Immunity & Infection Panorama©

I What molecular mechanisms protect our bodies from influenza virus infection? What events transpire when those defenses I I fail and infection occurs? Explore these questions and more with our Flu Flight: Immunity and Infection Panorama© created

by scientist, author and artist David Goodsell, PhD. ©

Influenza is a persistent health phenomenon that infects up to 10% (740 million) of the human populationRNA each year. These cellular, watercolor landscapes will take your students from infection of the ciliated epithelial cells that line the upperRP respiratory tract, through virus neutralization by antibodies in the mucosal barrier. Influenza – in the absence of antibodies – breaches the barrier and binds in the cellEpithelial membrane Cell Overview. In uenza before is a persistent fusing human health with threat. Ofthe endosomal membrane and finally releasing A the 7.4 billion people on earth, up to 10% (740 million people) are infected by M SCsegmented viral RNA genome into the cytoplasm.the in uenza virus each Illustrate year. While most peopleyour experience discussions only a mild form about infectious disease and immunity with this beautiful, accurate panorama that identifiesof the disease,key approximatelyproteins 4% (30 and million people) other develop molecular serious disease, structures and explains their functions! M2 leading to 250,000 - 500,000 deaths annually. These landscapes highlight the M1 HA molecular mechanisms whereby our immune system protects us from infection, and the molecular events that transpire when those defenses fail Tour of a Human Cell I See our Antibody and Antigen Models onand page an infection 17! occurs. Enhance your students’ conceptual understanding of immunity and This illustration simulates what we would see if we could K magnify a portion of a living cell by 1,500,000 times. At this H G magnication, atoms would be B about the size of a grain of salt, H infection with multiple models. Use the Antibody and Antigen Models (page 17) to actively simulate the antibody binding cells would be the size of huge buildings, and you would be In uenza viruses infect© the ciliated epithelial cells that line the upper © roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A and specificity illustrated in the Flu Fight Panoramarespiratory tract of humans.. Also When the virussee is inhaled, Tour it is initiallyof a trapped Human in Cell on the previous page. proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D the mucosal barrier that protects the ciliated epithelial cells in the respiratory Infection Panorama omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A D tract. Panel 1 shows an in uenza virus trapped in this mucosal© barrier – where The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to Immunity and Fight: Flu processing in the Golgi, and nishing with transport and secretion at the cell surface. C Flu Fight: Immunityit is neutralized & Infection by antibodies that Panorama are present due to a vaccine 23” or a xprevious 66” $59 (DGFFP) J C AP C B C D G virus infection. Panel 2 illustrates what happens if the mucosal© barrier is E G B Flu Fight: Immunitybreached & and Infection the virus reaches the Panorama surface of an epithelial cell.23” The xvirus 66” binds and 6-Antibody and M1 The Machinery of Life E F F This image is taken from The Machinery of Life by David S. J Goodsell. It reveals a previously unseen level of F A to glycoproteins embedded in the membrane of the cell, triggering uptake of biological scale. Light and electron microscopy may be used to explore the ultrastructure of cells, and X-ray B C crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried 12-Antigen Models Combo $355 (DGFFP-01-ANTPM-06) M2 molecules, but there is currently no way to observe the virus by receptor-mediated endocytosis. Panel 3 shows how the lower pH N directly the structure of living cells at the molecular level. To purchase this book, visit springer.com HA Instead, this illustration is synthesized by combining or your favorite bookseller. E experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics. of the endosome containing the virus induces a conformational change in the RNA

Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered structure of the hemagglutinin (HA) protein of the virus – leading ultimately to DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments the fusion of the viral and endosomal membranes (Panel 4) and the release of ...where molecules become real TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. In uenza Virus Infection Cycle R www.3dmoleculardesigns.com Flu Fight: Immunitythe & segmentedInfection viral RNA genome into the cytoplasm of the cell. Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 Panel 2 (below) - Docking and Receptor-Mediated Endocytosis of the In uenza Virus. In Panel 3 (top right) - pH-Induced Conformational Change in the Structure of the HA Protein. vATPases (V), located in the the absence of neutralizing antibodies, the neuraminidase (N) on the surface of the virus membrane of the endosome, pump protons into the endosome, which lowers the pH from ~pH 7 to ~pH 5. This drop in pH triggers a digests some of the carbohydrate chains on the mucin proteins, allowing the virus to penetrate conformational change in the structure of the HA proteins within in the viral membrane (VM), exposing the fusion peptides of the V deeper into the mucosal barrier and ultimately to the surface of ciliated epithelial cells. If IgA trimeric HA protein, which then embed themselves in the endosomal membrane (EM). EM Antibodies in Action antibodies have not neutralized the hemagglutinin (HA) protein on the surface of the virus, it binds to sialic acid receptor proteins (R) embedded in the surface of the epithelial cell. This Panel 4 (bottom right) - Membrane Fusion and Release of Viral RNA into the Cell. After the fusion peptides of the HA proteins Panel 1 - Antibodies in Action. The mucosal barrier that lines the ciliated epithelial cells of the upper respiratory tract in humans is composed of a thick network of triggers receptor-mediated-endocytosis wherein clathrin (C) and AP-2 (AP) proteins are embedded in the endosomal membrane, further conformational changes in the structure of HA brings the viral membrane closer proteins that works to trap and neutralize the virus, and to activate additional antiviral responses. Mucins (M) and IgA antibodies (A) are two kinds of proteins found in the spontaneously assemble into a geodesic dome-like structure and engulf the virus within a to the endosomal membrane. At the same time, protons ow into the virus through the M2 proton channel protein (M2), weakening HA mucosal barrier that limit access of the virus to the cell surface. Mucins are long, brous proteins that intertwine to create a thick, viscous network that nonspecically cellular membrane – creating an endosome. OtherRespiratory components of the in uenza virus include, the interaction between the matrix proteins (M1) and the viral RNA genome. As the viral membrane fuses with the endosomal I traps particulate matter and pathogens. IgA antibodies are produced in our adaptive immune system in response to either a vaccineIn uenza or a previous infection. They bind Mucosal M1 matrix protein (M1), M2 proton channel protein (M2), RNA polymerase (RP) and the membrane, the segmented viral RNA genome is released into the cytoplasm of the cell. This completes the rst stage of the VM Tour of a Human Cell primarily to regions of the hemagglutinin (HA) protein found on the surface of the in uenza virus, which blocks hemagglutinin from binding to the sialic acid receptor Endosomesegmented RNA genome. Epithelial in uenza virus infection cycle. proteins (R) on the surface of epithelial cells – the rst step in the in uenza virus infection process (Panel 2). The secretory component (SC) shown bound to dimeric IgA This illustration simulates what Virus Barrier we would see if we could K antibodies represents a protein involved in the transport of IgA proteins from the basal membrane of the epithelial cells to the apical membrane where it is secreted into magnify a portion of a living cell the mucosal barrier. Other proteins such as interferon (I) and lactoferrin (L) make up part of the innate immune system that activates other nonspecic antiviral defense Cell Cytoplasm by 1,500,000 times. At this H mechanisms. When viruses aren’t neutralized by antibodies, they attach to cells and begin endocytosis (Panels 2, 3 and 4). G magnication, atoms would be B about the size of a grain of salt, H cells would be the size of huge buildings, and you would be roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of I the smaller molecules have been I I A D omitted for clarity. In reality, the Scientist, author and artist David S. Goodsell, PhD, creates cellular landscapes that empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A accurately illustrate the size, shape and distribution of proteins in their natural D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G environment of the cell. His unique watercolor images connect the molecular world, RNA the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to RP processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C inferred by X-ray crystallography and NMR spectroscopy, with the cellular world, C B C D G observed by light and electron microscopy.Epithelial Cell Since Overview. In uenza 2009 is a persistent 3D Molecular human health threat. Of Designs has E G B A the 7.4 billion people on earth, up to 10% (740 million people) are infected by M SCmade several of Dr. Goodsell’s cellular thelandscapes in uenza virus each year. available While most people experience as large only a mild postersform for The Machinery of Life E of the disease, approximately 4% (30 million people) develop serious disease, F F leading to 250,000 - 500,000 deaths annually. These landscapes highlight the M2 This image is taken from The Machinery of Life by David S. classroom use. Dr. Goodsell’s books, (2010) and M1 J Themolecular Machinery mechanisms whereby our ofimmune Life system protects us from Atomic Goodsell. It reveals a previously unseen level of F A HA biological scale. Light and electron microscopy may be infection, and the molecular events that transpire when those defenses fail used to explore the ultrastructure of cells, and X-ray B Evidence: Seeing the Molecular Basisand an infectionof Life occurs. (2016), are available from major crystallography and NMR spectroscopy may be used to L reveal the atomic structure of individual puried In uenza viruses infect the ciliated epithelial cells that line the upper molecules, but there is currently no way to observe booksellers. directly the structure of living cells at the molecular level. To purchase this book, visit springer.com respiratory tract of humans. When the virus is inhaled, it is initially trapped in Instead, this illustration is synthesized by combining or your favorite bookseller. E the mucosal barrier that protects the ciliated epithelial cells in the respiratory experimental data on cellular ultrastructure, the atomic tract. Panel 1 shows an in uenza virus trapped in this mucosal barrier – where structure of molecules, and bioinformatics. it is neutralized by antibodies that are present due to a vaccine or a previous AP virus infection. Panel 2 illustrates what happens if the mucosal barrier is breached and the virus reaches the surface of an epithelial cell. The virus binds M1 Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered Golgi Apparatus. to glycoproteins embedded in the membrane of the cell, triggering uptake of DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that C M2 wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) the virus by receptor-mediated endocytosis. Panel 3 shows how the lower pH HA N and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. of the endosome containing the virus induces a conformational change in the RNA read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments structure of the hemagglutinin (HA) protein of the virus – leading ultimately to TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real the fusion of the viral and endosomal membranes (Panel 4) and the release of R the segmented viral RNA genome into the cytoplasm of the cell. www.3dmoleculardesigns.com

Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 Respiratory In uenza Mucosal Endosome Epithelial Virus Barrier Cell Cytoplasm

Scientist, author and artist David S. Goodsell, PhD, creates cellular landscapes that accurately illustrate the size, shape and distribution of proteins in their natural cbm.msoe.edu environmentwww. of the cell. His3dmolecula unique watercolor images connect ther desimolecular world,g ns.com inferred by X-ray crystallography and NMR spectroscopy, with the cellular world, observed by light and electron microscopy. Since 2009 3D Molecular Designs has made several of Dr. Goodsell’s cellular landscapes available as large posters for classroom use. Dr. Goodsell’s books, The Machinery of Life (2010) and Atomic Copyright 3D Molecular Designs - All Rights Reserved Version 1.0 - 3/2017 L Evidence: Seeing the Molecular Basis of Life (2016), are available from major booksellers.

...where molecules become real TM

www.3dmoleculardesigns.com Copyright 3D Molecular Designs - All Rights Reserved - 2017, 2018 Version 1.1 Mitochondria and E. coli Posters

M © Unlike simpler bacterial cells, E. coli our cells are lled with compartments that perform dierent duties. ATP synthesis is In the Mitochondria Poster (left) your students will see the the primary task performed by the mitochondria, shown here in cross section at 2,500,000 magni cation. The enzymes of the citric acid cycle (A) are found in the innermost space, termed the matrix. The inner membrane, which is folded into complicated large protein complexes of the electron transport chain which shapes, is densely packed with the large protein complexes of the electron transport chain (B), which create the electrochemical gradient that powers ATP synthase (C) to build ATP. The ATP is then transported out of the mitochondrion by the create the electrochemical gradient that powers ATP synthase E adenine nucleotide translocator (D) and nally diuses through channels in the VDAC protein (E) in the outer membrane. The space between the membranes is lled with cytochrome c (F), enzymes such as creatine kinase (G) that are involved in energy to build ATP. ATP is then transported out of the mitochondrion metabolism, as well as several proteins involved in programmed cell death. Each mitochondrion also includes a full set of machinery for synthesizing proteins, including Bacteria are microorganisms that are found in most DNA (H), RNA polymerase (I), habitats on the Earth. The bacterium shown above ribosomes (J), and transfer RNA (70,000 X) is Escherichia coli. It is found in the lower digestive (K). It does not make all of its by the adenine nucleotide translocator and diffuses through system, and is also one of the most well-studied organisms. own proteins, however, and It has a relatively simple overall structure. It is surrounded some must be imported from by a cell wall composed of two membranes (in green). the cytoplasm by specialized Several long corkscrew-shaped agella are turned by transport proteins (L) in the molecular motors embedded in the cell wall, propelling the inner and outer membranes. bacterium through its environment. The DNA and other genetic machinery are loosely arranged into a nucleoid Posters inside the cell (in yellow and orange). The remaining space The Machinery of Life the channels in the VDAC protein in the outer membrane. is lled with many soluble molecular machines such as This image is taken from The enzymes and ribosomes (in blue and purple) that build Machinery of Life by David S. new molecules, harness sources of energy, and sense and Goodsell. It reveals a previously protect the bacterium from dangers in its environment. unseen level of biological scale. Light and electron microscopy may be used to explore the Looking at a close-up of one portion of the cell ultrastructure of cells, and X-ray (3,000,000 X), we can see the many macromolecules crystallography and NMR performing their functions. The large agellar motor, which spectroscopy may be used to is powered by the ow of hydrogen ions across the inner reveal the atomic structure of membrane, dominates the scene. An array of sensory individual puri ed molecules, © molecules monitors the levels of nutrients and decides but there is currently no way to when to turn the agellum and move to a better observe directly the structure of environment. Many other proteins embedded in the living cells at the molecular membrane control the ow of molecules in and out of the level. Instead, this illustration is cell, and long sugar chains extend from the outer surface, synthesized by combining The E. coli Poster (right) illustrates the inside of an E. coli protecting the cell. Inside the cell, there are many experimental data on cellular ribosomes building proteins, based on messenger RNA ultrastructure, the atomic transcribed from the DNA by RNA polymerase. A molecule F structure of molecules, and of DNA polymerase is also shown, replicating the DNA. bioinformatics. Enzymes of glycolysis and the citric acid cycle are breaking down food molecules and capturing the energy, and synthetic enzymes are building all of the other molecules cell — magnified 1 million times. The molecular complexity of that the cell needs. coli E. CC this bacterial cell is emphasized in this image which features a

To purchase this book, visit springer.com or your favorite bookseller. large flagellum and the motor proteins that power its rotation The Machinery of Life This image is taken from The Machinery of Life by David S. Goodsell. It reveals a previously unseen level of biological scale. Light and electron microscopy may be used to explore the ultrastructure of cells, and X-ray and a variety of transmembrane proteins that function in crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried molecules, but there is currently no way to observe directly the structure of living cells at the molecular level. Instead, this I illustration is synthesized by combining experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics. transporting molecules into and out of the cell. Also shown are To purchase this book, visit springer.com or your favorite bookseller. I the ribosomes and associated proteins that support bacterial

...where molecules become real TM ...where molecules become real TM 3dmoleculardesigns.com 3dmoleculardesigns.com

Copyright 3D Molecular Designs protein synthesis and the DNA, along with the DNA and RNA All Rights Reserved - 2009, 2016, 2018 Version 1.2 Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 polymerases that function in replication and transcription. Version 1.2 Mitochondria Poster© E. coli Poster© Mitochondria Poster© 23” x 30” $29 (DGMP) • E. coli Poster© 23” x 30” $29 (DGECP) Mitochondria and Also see Tour of a Human Cell© (page 14), the Dynamic DNA Kit© (page 11) and the following mini models: Nucleosome, Ribosomes and tRNA (page 16), Antibody, Hemagglutinin and Influenza Virus Capsule (page 17).

3dmoleculardesigns.com 15 ...where molecules become real TM

Spring 2019 Nucleosome Mini Model Nucleosome Nucleosome Mini Model Mini The nucleosome is the most basic, repeating structural unit of chromosomes. Its central protein core has 8 histones (2 copies each of H2A, H2B, H3 and H4) and 145 base pairs of double- stranded DNA. The N-terminal end of each histone has many positively-charged amino acids that interact with the negatively-charged phosphate backbone of DNA. This model reveals that histones interact only with the minor groove of DNA. The major groove is then available for sequence-specific DNA binding proteins, such as Zif 268. 4” Plaster Model $252 (NCSMM) ! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Large and Small Ribosome Mini Models Ribosome Mini Models Mini Ribosome Protein synthesis becomes understandable as your students see the 3 tRNAs of the small (30S) Large and Small Large and Small subunit and how they fit into the cavity of the large subunit (50S) to synthesize proteins. In the large subunit, they will see the single adenosine base (yellow) that catalyzes formation during protein synthesis. Newly synthesized protein exits the ribosome through a visible channel that extends from the catalytic adenosine to the surface of the ribosome. The small subunit (30S) folds into a specific 3-D structure and is stabilized by associated proteins. In this spacefilled model, two tRNAs (green) dock with their 3’ends close together —­ ready for peptide bond formation. Pair $450 (R5030SMM) • 4” 50S Ribosome $272 (R50SMM) • 4” 30S Ribosome $232 (R30SMM)

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Transfer RNA Mini Model Transfer RNA Mini Models Mini Transfer RNA (tRNA) is a short RNA molecule (76 nucleotides) that delivers amino acids to the ribosome, where they join a growing chain during protein synthesis. Transfer RNAs fold into 3-D structures, stabilized by hydrogen bonding between complementary bases. 3.5” Plaster Model $76 (TRNAMM) ! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

© © Also see Dynamic DNA Kit (page 11), Flow of Genetic Information Kit (page 12) and Tour of a Human Cell© (page 14). 3DMD Genetic Codon Posters©

The Genetic Codon Chart© and Genetic Codon Circle© can The Genetic Codon Circle © 3

G be used with 3DMD’s popular Amino Acid Starter Kit , L Gly © © Phe β Glu Leu C A G D Glycine S Glutamic Acid

-Globin Folding Kit and Insulin mRNA to Protein Kit — Phenylalanine Asp Leucine Ser Codon Posters Phe C Ser S A Tyr G Cys C Aspartic Acid A G C

3DMD Genetic 3DMD Genetic C A Serine G G C Phe CC Ser S AC Tyr GC Cys C C which introduce your students to a standard color scheme: A C A C A Tyr Ala A Leu L CA Ser S AA Stop GA Stop A G Tyrosine Alanine G G Leu L CG Ser S AG Stop GG Trp G hydrophobic amino acids are yellow, polar amino acids are A G C STP C A C A G C Arg Cysteine Cys C Leu L CC Pro P CA His H CG white, acidic amino acids are red, basic amino acids are blue G C A al aline A C CC Leu L CCC Pro P CAC His H CGC Arg C STP C A CA CCA CAA Gln Arg A and cysteines are green. Students can easily build a seamless G G Tryptophan Trp C Leu L Pro P CGA 3 G 3 G CG Leu L CCG Pro P CAG Gln CGG Arg G Arginine Arg A C connection between the triplet codon in mRNA and the G Leucine C A Leu L A Ile I AC Thr T AA Asn N AG Ser S Serine A C G chemical property of the amino acid it encodes. S Ser G AC Ile I ACC Thr T AAC Asn N AGC Ser S C A A C C Lysine C A Proline A AA Ile I ACA Thr T AAA Lys AGA Arg A Lys © C A G Pro Asparagine G AG Met M ACG Thr T AAG Lys AGG Arg G A G C P C A Histidine Genetic Codon Chart (24” x 30”) $24 each (GCCA) Asn G N G A C Glutamine His G al GC Ala A GA Asp D GG Gly G © Threonine C G A

Arginine Gln H Thr Methionine © GC GCC GAC Asp D GGC Gly G C al Ala A Isoleucine Genetic Codon Circle (30” x 24”) $24 each (GCCB) Arg T Gly G Met G GA al GCA Ala A GAA Glu GGA A Ile M GG al GCG Ala A GAG Glu GGG Gly G G © I Amino Acid Properties Best when used with the Amino Acid Starter Kit and Amino 3 © © Amino Acid Properties Translation Start Codon Hydrophobic Non-polar Negatie Charge Cysteine β Translation Start Codon STP Translation Stop Codon ...where molecules become real TM Acid Starter Kit Poster (Page 7), -Globin Folding Kit and Map Translation Stop Codon Hydrophilic Polar Positie Charge Hydrophilic Polar Negatie Charge 3eaeg ...where molecules become real TM β Hydrophobic Non-polar Positie Charge 3eaeg Copyright 3D Molecular Designs - All ights esered - 2 21 21 ersion . Copyright 3D Molecular Designs - All ights esered - 2 21 21 ersion . of the Human -Globin Gene (page 6), Insulin mRNA to Protein Cysteine © © © Kit (page 9) and Flow of Genetic Information Kit (page 13). The Genetic Codon Chart The Genetic Codon Circle©

16 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM

Antibody and Antigen Models

Incorporate the concepts of protein structure and function while teaching the immune system using our antibody model – now printed in more durable plastic. Antibodies Flu Fight: Immunity & Infection In uenza Virus Infection Cycle arePanel 2 (below) - composedDocking and Receptor-Mediated Endocytosis of the In uenza Virus. of In 12Panel 3 (top right) repeating - pH-Induced Conformational Change in the Structure of the HAimmunoglobulin Protein. vATPases (V), located in the folds. Our model highlights the four the absence of neutralizing antibodies, the neuraminidase (N) on the surface of the virus membrane of the endosome, pump protons into the endosome, which lowers the pH from ~pH 7 to ~pH 5. This drop in pH triggers a digests some of the carbohydrate chains on the mucin proteins, allowing the virus to penetrate conformational change in the structure of the HA proteins within in the viral membrane (VM), exposing the fusion peptides of the V deeper into the mucosal barrier and ultimately to the surface of ciliated epithelial cells. If IgA trimeric HA protein, which then embed themselves in the endosomal membrane (EM). EM Antibodies in Action antibodies have not neutralized the hemagglutinin (HA) protein on the surface of the virus, it binds to sialic acid receptor proteins (R) embedded in the surface of the epithelial cell. This Panel 4 (bottom right) - Membrane Fusion and Release of Viral RNA into the Cell. After the fusion peptides of the HA proteins Panel 1 - Antibodies in Action. The mucosal barrier that lines the ciliated epithelial cells of the upper respiratory tract in humans is composed of a thick network of polypeptidestriggers receptor-mediated-endocytosis wherein clathrin (C) and AP-2 (AP) proteins – twoare embedded yellow in the endosomal membrane, further conformationalheavy changes in the structure of HAchains brings the viral membrane closer and two red light chains – that join to form the proteins that works to trap and neutralize the virus, and to activate additional antiviral responses. Mucins (M) and IgA antibodies (A) are two kinds of proteins found in the spontaneously assemble into a geodesic dome-like structure and engulf the virus within a to the endosomal membrane. At the same time, protons ow into the virus through the M2 proton channel protein (M2), weakening HA mucosal barrier that limit access of the virus to the cell surface. Mucins are long, brous proteins that intertwine to create a thick, viscous network that nonspecically cellular membrane – creating an endosome. Other components of the in uenza virus include, the interaction between the matrix proteins (M1) and the viral RNA genome. As the viral membrane fuses with the endosomal traps particulate matter and pathogens. IgA antibodies are produced in our adaptive immune system in response to either a vaccine or a previous infection. They bind M1 matrix protein (M1), M2 proton channel protein (M2), RNA polymerase (RP) and the membrane, the segmented viral RNA genome is released into the cytoplasm of the cell. This completes the rst stage of the VM primarily to regions of the hemagglutinin (HA) protein found on the surface of the in uenza virus, which blocks hemagglutinin from binding to the sialic acid receptor segmented RNA genome. in uenza virus infection cycle. proteins (R) on the surface of epithelial cells – the rst step in the in uenza virus infection process (Panel 2). The secretory component (SC) shown bound to dimeric IgA iconic “Y” shaped molecule. Students will model how an antibody binds to two antigens antibodies represents a protein involved in the transport of IgA proteins from the basal membrane of the epithelial cells to the apical membrane where it is secreted into the mucosal barrier. Other proteins such as interferon (I) and lactoferrin (L) make up part of the innate immune system that activates other nonspecic antiviral defense mechanisms. When viruses aren’t neutralized by antibodies, they attach to cells and begin endocytosis (Panels 2, 3 and 4). (purple globular structures) found on an influenza virus protein. I

I I

RNA Enhance your students’ conceptual understanding of immunity and RP

Epithelial Cell Overview. In uenza is a persistent human health threat. Of infection with multiple models. Use the Antibody and Antigen Models to A the 7.4 billion people on earth, up to 10% (740 million people) are infected by M SC the in uenza virus each year. While most people experience only a mild form of the disease, approximately 4% (30 million people) develop serious disease, M2 leading to 250,000 - 500,000 deaths annually. These landscapes highlight the M1 HA molecular mechanisms whereby our immune system protects us from infection, and the molecular events that transpire when those defenses fail actively simulate the antibody binding and specificity illustrated in the and an infection occurs.

In uenza viruses infect the ciliated epithelial cells that line the upper © andAntibody respiratory tract of humans. When the virus is inhaled, it is initially trapped in

the mucosal barrier that protects the ciliated epithelial cells in the respiratory Models Antigen tract. Panel 1 shows an in uenza virus trapped in this mucosal barrier – where Flu Fight: Immunity & Infection Panorama (page 15). it is neutralized by antibodies that are present due to a vaccine or a previous AP virus infection. Panel 2 illustrates what happens if the mucosal barrier is breached and the virus reaches the surface of an epithelial cell. The virus binds M1 to glycoproteins embedded in the membrane of the cell, triggering uptake of C the virus by receptor-mediated endocytosis. Panel 3 shows how the lower pH HA N M2 of the endosome containing the virus induces a conformational change in the RNA structure of the hemagglutinin (HA) protein of the virus – leading ultimately to the fusion of the viral and endosomal membranes (Panel 4) and the release of 1 8.5” Plastic Antibody and 2 3.5” Antigen Models $55 (ANTPM) R the segmented viral RNA genome into the cytoplasm of the cell.

Respiratory In uenza Mucosal Endosome Epithelial © Virus Barrier Cell Cytoplasm Flu Fight: Immunity & Infection Panorama 23” x 66” and 6-Antibody and

Scientist, author and artist David S. Goodsell, PhD, creates cellular landscapes that accurately illustrate the size, shape and distribution of proteins in their natural environment of the cell. His unique watercolor images connect the molecular world, inferred by X-ray crystallography and NMR spectroscopy, with the cellular world, observed by light and electron microscopy. Since 2009 3D Molecular Designs has made several of Dr. Goodsell’s cellular landscapes available as large posters for 12-Antigen Models Combo $355 (DGFFP-01-ANTPM-06) classroom use. Dr. Goodsell’s books, The Machinery of Life (2010) and Atomic L Evidence: Seeing the Molecular Basis of Life (2016), are available from major Flu Fight: Immunitybooksellers. & Infection Panorama© ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 cbm.msoe.edu www.3dmoleculardesigns.com Please see bottom of page 2 for details. Copyright 3D Molecular Designs - All Rights Reserved Version 1.0 - 3/2017 Hemagglutinin Mini Model

The hemagglutinin protein (HA) of the influenza virus plays a critical role in the infection process. These models show the dramatically different shapes of the hemagglutinin HA2 protein at pH 7 and at pH 5. Tell the amazing molecular story of how the virus takes advantage of the dramatic decrease in pH following the uptake of the virus by receptor- mediated endocytosis. Color coding enables students to clearly see the conformational changes that the protein undergoes. This model can be used in conjunction with the Tour of the Human Cell© (page 14) that illustrates a ß-cell that has been stimulated to produce Mini Model antibodies in response to the flu vaccine. Hemagglutinin 6.5” Tall Plaster Mini Model $114 (HAMM)

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

Influenza Virus Capsules

Influenza is an RNA virus with a roughly spherical lipid envelope. The outside of the virus capsule is covered with 3 specific proteins: hemagglutinin (HA), neuraminidase (NA) and the M2 channel. These proteins are involved in virus docking, endocytosis and fusion of the viral membrane to the host cell; the release of newly budded virus from infected cells; and acidification of the virus core and release of the segmented viral RNA. The specific sub-types and combinations of the hemagglutinin (H) and neuraminidase (N) on the surface of the virus capsule categorize the strain of the virus. The viral RNA is represented by 8 segments of RNA

that represent a re-assorted virus emerging from a host cell simultaneously infected with a Capsules

swine flu virus and an avian flu virus (H1N1 swine flu). Virus Influenza 6’’ Plaster Model $625 (IVCM6) • 4” Plaster Mini Model $450 (IVCM4) 6” Plaster Model is not eligible for discounts

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

Also see Tour of a Human Cell© (page 14). Use Nucleosome, Ribosomes, tRNA, Antibody, Hemagglutinin and Influenza Virus Capsule with the Tour of a Human Cell© to tell the story of a flu shot in action.

3dmoleculardesigns.com 17 ...where molecules become real TM

Spring 2019 w Neurotransmitters Module: The Beery Twins’ Story© A Project-Based Learning Activity Engage your students and cover a wide-range of science topics with the true story of California twins Noah and Alexis Beery, who have gene variants that cause them to have life-threatening low levels of three neurotransmitters. Whole genome sequencing in 2010 identified a mutation in the gene that encodes the sepiapterin reductase enzyme, leading to a molecular diagnosis and successful treatment. Human Sepiapterin Reductase mRNA Gene Map© Reductase mRNA Gene Map mRNA Gene Reductase This gene map presents the nucleotide sequence of the messenger RNA encoding sepiapterin

Human Sepiapterin Human Sepiapterin reductase – the enzyme that was shown to be defective in Noah and Alexis Beery. The map documents the molecular consequence of two different mutations in this gene that were responsible for the neurotransmitter deficiencies experienced by the Beery twins. Teacher notes and student handouts are available online. 1 Student and 1 Teacher Human SPR mRNA Gene Map $19 (SPRGM-01S-01T) 3 Student and 1 Teacher Human SPR mRNA Gene Map $40 (SPRGM-03S-01T) 6 Student and 1 Teacher Human SPR mRNA Gene Map $75 (SPRGM-06S-01T) ©

Sepiapterin Reductase Mini Model Sepiapterin Reductase Reductase Sepiapterin Show your students a physical representation of the twins’ genetic mutations and neurotransmitter deficiencies with the Sepiapterin

Mini Model Mini Reductase Mini Model. Three small, magnet-docked sections of the model are removable, revealing the two mutations that the twins inherited from their parents and the cofactor needed for the production of the neurotransmitters. A placemat and other Dad’s Mutation supporting materials are available online. ! WARNING: CHOKING HAZARD Sepiapterin Reductase ! WARNING: SMALL MAGNETS Mini Model $137 (SPRMM) CAUTION: Science Education Product ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details. Cofactor Mom’s Mutation Dopamine and Serotonin Biosynthesis Models Dopamine and Serotonin Dopamine and Serotonin

Biosynthesis Models These models show how two amino acids (tyrosine and tryptophan) are converted into two neurotransmitters (dopamine and serotonin) by two consecutive enzyme-catalyzed reactions. Magnet-docked hydroxyl groups, carboxylate groups and hydrogens allow each model to be quickly converted from amino acid to neurotransmitter in two easy steps. Placemats and supporting materials are available online. Dopamine Biosynthesis Model 3” Dopamine Biosynthesis Model $37 (DBMM) 3” Serotonin Biosynthesis Model $39 (SBMM) ! WARNING: CHOKING HAZARD © © Serotonin Biosynthesis Model Also see Dynamic DNA Kit (page 11), Flow of Genetic Information Kit (page ! WARNING: SMALL MAGNETS 13), DNA Starter Kit© (page 20) and Tour of a Human Cell© (page 14). CAUTION: Science Education Product ! WARNING: CALIFORNIA PROP 65 Please see bottom of page 2 for details. The gene map, Sepiaterin Reductase Mini Model and biosynthesis models may be used separately or together to meet the needs of your classroom.

18 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM w Synapse Construction Kit©

Engage your classroom with hands-on modeling of neuronal communication! Students can use the colorful foam pieces in our Synapse Construction Kit© to: • Discover how the resting potential of a neuron is established. • Demonstrate the propagation of an action potential down an axon. © • Simulate the action of the sodium-potassium pump in resetting the resting potential. • Explore the effects of neurotransmitters acetylcholine, dopamine and GABA on a post synaptic neuron. • Model cholinergic, dopaminergic and GABAergic synapses. • Compare and contrast metabotropic and ionotropic receptors. • Analyze the impact of various substances such as nicotine, cocaine, sarin gas and propofol on neuronal signaling. Assembly Instructions, lessons and activities are available online at 3dmoleculardesigns.com/Teacher-Resources.htm.

1-Group Set $120 (SCK-01) • 3-Group Set $330 (SCK-03) • 6-Group Set $630 (SCK-06) Kit Construction Synapse Also see Phospholipid & Membrane Transport Kit© (page 5) and Neuron Modeling Kit© (below).

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Neuron Modeling Kit©

Captivate your classroom and explore multiple concepts with our large and ©

small foam neuron models! Students can use the Neuron Modeling Kit to: © • Construct a model and identify parts of a multipolar neuron. • Distinguish between multipolar neurons, bipolar neurons, unipolar neurons and interneurons, and determine their location and function in the human body. • Use myelin sheath pieces to show differences between two types of neuroglia in the central and peripheral nervous systems. • Construct simple and complex neural pathways and examine the effect on neuronal firing at excitatory and inhibitory synapses. Lessons and activities are available online at 3dmoleculardesigns.com/Teacher-Resources.htm. Modeling Kit Neuron Dopamine and Serotonin Biosynthesis Models Neuron Modeling Kit© $39 (NMK-01) Amino Acid Building Block Models

These Amino Acid Building Block Models from Molymod® enable your students to explore the basic structure of amino acids — the building blocks of proteins. The kit contains all of the atoms and bonds needed to construct 2 models of a generic amino acid. Side chains are represented by the green spheres. The 2 amino acids can be joined by a peptide bond to make a dipeptide — splitting out a water molecule. Activities for using the models are available online. ! WARNING: CHOKING HAZARD Amino Acid Building Block Models $15 (AABB) Block Models CAUTION: Science Education Product © Please see bottom of page 2 for details. Also see Amino Acid Starter Kit (page 7). Amino Acid Building Acid Amino

3dmoleculardesigns.com 19 ...where molecules become real TM

Spring 2019 Alpha Helix & Beta Sheet Models

The alpha helix and the beta sheet represent the 2 important protein structural

Beta Sheet Models Beta elements of secondary protein structure. We feature 4 models for your students to

Alpha Helix & Alpha Helix & explore — 2 alpha helix and 2 beta sheet models. Both alpha sheet plaster models are derived from helix E of the β-globin (amino Alpha Helix without Side Chains Beta Sheet without Side Chains acids 58-74) protein, which consists predominantly of alpha helices. Both beta sheet plaster models are derived from amino acids 14-32 and 120-127 of green fluorescent protein. Two strands are parallel and 2 strands are anti-parallel. 4.5” Alpha Helix without Side Chains $75 (AH) 4.75” Alpha Helix with Side Chains $149 (AHS) 6.5” Beta Sheet without Side Chains $151 (BS) 7” Beta Sheet with Side Chains $281 (BSS) β Also see -Globin Mini Models (page 6), Green Fluorescent Protein Mini Model (page 21) Alpha Helix with Side Chains Beta Sheet with Side Chains and Alpha Helix & Beta Sheet Construction Kit (below).

! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. Alpha Helix & Beta Sheet Alpha Sheet Helix & Beta ©

Construction Kit Alpha Helix & Beta Sheet Construction Kit

This 3D-printed kit allows your students to build each of 2 important protein secondary structures an alpha helix and a beta sheet. After joining together the magnetic backbone amino acid units to form the 2 structures, your students will actually feel the stabilizing effect of the hydrogen bonds as they are added to the backbone units. Then your students can add amino acid side chains, modeling specific alpha helices and beta sheets. Alpha Helix & Beta Sheet Construction Kit© $495 (AHBSCK) © Also see Dynamic DNA Kit© (page 11), Flow of Genetic Information Kit© (page 13) and Tour of a Human Cell© (page 14). ! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details. DNA Starter Kit©

Engage your students with this interactive, foam model of double- stranded DNA and single-stranded RNA. The DNA Starter Kit© is a schematic model that transforms from the familiar ladder shape to the double helix with a twist. Your students can explore DNA Starter Kit DNA Starter the structure of color-coded DNA bases showing purines and pyrimidines connected to a continuous sugar-phosphate backbone. Then they can explore the process of DNA replication and RNA transcription. Turn the nucleotide monophosphates into nucleotide triphosphates with the Triphosphate Expansion Pack.

Each 1-group set includes 51 bases (12 red adenine, 12 yellow

© thymine, 12 blue cytosine, 12 green guanine, 3 white uracil), 4 continuous gray backbones, 24 gray sugar-phosphates and 12 lavender sugar-phosphates. 2-Group Set $62 (DNASK-02) • 1-Group Set $34 (DNASK-01) Triphosphate Expansion Pack $15 (DNASK-PEP)

! WARNING: CHOKING HAZARD Nucleotide Triphosphates CAUTION: Science Education Product Please see bottom of page 2 for details.

20 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightly or handled roughly. ...where molecules become real TM

Modeling as a Practice of Science The Next Generation Science Standards emphasize the important role of modeling — both as an integral practice of science and as an important learning tool for students. 3D Molecular Designs offers 2 instructional tools, The Data Dilemma© and the Mystery Tube©, to engage students in an active modeling experience, while introducing them to the practice of science using logic, evidence and reasoning. © The Data Dilemma ©

While using The Data Dilemma© your students will experience the dilemma scientists face when new data indicates the mental model of the object they are researching needs to be modified. As each new data set is introduced and your students form a series of new models — using foam tangram pieces — your students will learn that the practice of science is an ongoing process, not a set of facts published in a textbook or online. How many possible models can your students find? Teacher notes are available online. 12-Puzzle Set $24 (DD-12) The Data Dilemma Data The Mystery Tube©

The Mystery Tube© introduces your students to the practice of science. Research scientists © frequently face the challenge of examining an object or organism without taking it apart. As your students first pull the cord on one end and the other end pulls into the tube, they may think the solution is easy. But wait, as they continue their investigation, they will be challenged to describe a model for the inner workings of the Mystery Tube© and provide supporting evidence to defend their hypothesis. Teacher notes and student handouts are available online. Activities for using the models are available online. Mystery Tube Mystery 12-Tube Set $114 (MTAB-12) • 6-Tube Set $61 (MTAB-06) • 2-Tube Set $23 (MTAB-02) Modeling Mini Toobers

Versatile mini toobers provide hands-on learning experiences in many science disciplines. Biology and chemistry students can model DNA or create protein structures while following the principles of chemistry. Physics students can explore sound and other waves. The flexible foam mini toobers have a soft wire core and are 4’ long. One red and one blue end cap is included with each mini toober. Use end caps to designate N terminus and C terminus in protein-folding or 3’ and 5’ ends in DNA model. Push Pins Are Not Included. 3DMD’s protein folding activity is available online. 4’ Toober $10 (MTBR-01) Also see Amino Acid Starter Kit© (page 7). Modeling Mini Toobers ! WARNING: CHOKING HAZARD CAUTION: Science Education Product Please see bottom of page 2 for details. Green Fluorescent Protein Mini Model

Green Fluorescent Protein (GFP) is responsible for the green bioluminescence of many marine organisms, including Pacific Northwest jellyfish. Its structure consists of an 11-stranded beta barrel surrounding a central alpha helix containing the fluorophore that emits light. The backbone is color-coded for students to follow the folding of the protein from its amino- to its carboxy-terminus. It is an excellent tool when teaching protein structure and biotechnology. 3.5” Plaster Model $112 (GFPMM) © Green Fluorescent Fluorescent Green Also see Amino Acid Starter Kit (page 7). Mini Model Protein ! WARNING: CHOKING HAZARD CAUTION: Science Education Product ! WARNING: CALIFORNIA PROPOSITION 65 Please see bottom of page 2 for details.

3dmoleculardesigns.com 21 ...where molecules become real TM

Spring 2019 STEM and Next Generation Science Standards

3D Molecular Designs’ kits and models focus on core ideas and cross-cutting concepts in biology, chemistry, physical and life sciences. Products, lessons and activities fit STEM curriculum that blend science, technology, engineering and math – and curriculum designed to support Next Generation Science Standards (NGSS), which emphasize the important role of models (and modeling) as an authentic practice of scientists and engineers. Connections to the NGSS Framework for K-12 Science Education Practices: Crosscutting Concepts, and Core Ideas can be found with the teacher resources for each product at 3dmoleculardesigns.com/Teacher-Resources.htm.

Stay Connected We Moved! Our new address: Sign up to receive our monthly email newsletter and stay up-to-date 804 N. Milwaukee St. about 3D Molecular Designs’ latest products and events! Suite 200 Milwaukee, WI 53202 We Appreciate Your Feedback!

Please let others know how a 3DMD product worked for your students by posting a review on our website. Have you developed a great activity for one of our kits or models? Consider sharing your lessons, assessments or videos with us so we can share them with other teachers! Wish List Page No. Product Code Product Name Price Quantity Total

Place your order online with a credit card or a purchase order at shop3dmoleculardesigns.com, email [email protected], fax 1-414-774-3435 or call 414-774-6562. Please provide your tax exempt number if applicable. Find and print our order form at 3dmoleculardesigns.com/catalog.htm. We are happy to provide quotes. You can generate your own quote by adding items to your shopping cart and entering your shipping address. Or, send us an email or give us a call. Shipping rates vary based on box size, weight and destination. We can provide either United Parcel Service or U.S. Postal Service for delivery, to help ensure the most cost-effective and reliable service possible. Customers in Canada should contact us for shipping costs. 3D Molecular Designs cannot ship to all countries. Don’t have enough resources to buy classroom materials? Find information about grants and fundraising opportunities at 3dmoleculardesigns.com/Ordering-Information.htm. 22 ...where molecules become real TM

Science Olympiad Protein Modeling Event Kits

Even bacteria get infected with viruses! The 2018-2019 Science Olympiad Protein Modeling event explores one way bacteria combat viral infections. Using CRISPR (clustered regularly interspersed palindromic repeats) and Cas proteins, bacteria recognize viral DNA and chop it into pieces. Viruses counterattack using AntiCRISPR. This season’s protein modeling event examines the structures of CRISPR and AntiCRISPR – the war on bugs! Visit cbm.msoe/edu/scienceOlympiad for resources to help hone your protein structure and modeling skills. The materials in the Pre-Build Kit can be reused for each competition this season. The 2018-2019 Pre-Build Kit is based on residues 1-85 of chain B of 5vw1.pdb. The Practice Kit simulates the competition environment and is modeled after the 2015-2016 Regional On-Site Competition. Order Pre-Build and Practice Kits by May 15, 2019 and save 15%! The best preparation for understanding protein structure and function is our Amino Acid Starter Kit©. Purchase our Pre-Build Kit and Amino Acid Starter Kit Bundle© for $78.20 and save 15% (regularly priced $92!).

Tournament directors and event supervisors, visit 3dmoleculardesigns.com/ Science-Olympiad-Protein-Modeling-Kits.htm for information about ordering Invitational On-Site Kits. Sign up to receive Regional and State On-Site Kits, Exams and Judging Materials free of charge. Pre-Build Kit $29 (SOPB19) Practice Kit $23 (SOPK18-19) Practice Judging Model $40 (SOPJM) Pre-Build Kit and Amino Acid Starter Kit© Bundle $92 (SOAA)

! WARNING: CHOKING HAZARD Kits Modeling Event Olympiad Protein Science ! WARNING: SMALL MAGNETS CAUTION: Science Education Product Please see bottom of page 2 for details.

© Pre-Build Kit and Amino Acid Starter Kit Bundle PROFESSIONAL DEVELOPMENT OPPORTUNITIES

Work with the organization behind some of your favorite 3DMD products to: Help create innovative instructional materials that make the molecular world come alive for students. Gain the experience to confidently use active-learning tools in your classroom.

3D Molecular Designs’ sister organization – the Milwaukee School of Engineering (MSOE) Center for BioMolecular Modeling (CBM) – offers summer professional development courses that connect the big ideas of chemistry and biology with stories of current research, using physical models of proteins and other molecular structures. CBM staff guide teachers in the exploration of hands-on teaching tools. Workshop participants also help refine instructional materials that are still in development.*

Visit cbm.msoe.edu for more information about the CBM and the professional development courses they offer.

Center for BioMolecular Modeling 1025 N. Broadway Street Milwaukee, WI 53202-3109 (414) 227-7529 *Also look for CBM and 3DMD workshops at regional and national science education conferences throughout the year.

3dmoleculardesigns.com 23 ...where molecules become real TM

“It’s the whole picture! It’s the whole deal!” © NEW Dynamic DNA Kit

Students Discover • Accurate DNA and RNA • Nucleotide base pairing • Semi-conservative replication • Continuous & discontinuous strands • RNA transcription • 5’ to 3’ synthesis • Major and minor grooves • Phosphodiester bonds • DNA packaging • Adenosine triphosphate See page 11.

NEW Tour of a Human Cell© 1-Grand Panorama and 6-Panoramas Combo “Textbooks don’t give the view of the complexity and design of the cell that this landscape does!”

Tour of a Human Cell I

This illustration simulates what we would see if we could K magnify a portion of a living cell by 1,500,000 times. At this H G magnication, atoms would be B about the size of a grain of salt, H cells would be the size of huge buildings, and you would be roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules in the cell are shown, including A proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, and many other small molecules. A D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated to the production of antibodies. The entire process of antibody production is shown, starting from I G the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to processing in the Golgi, and nishing with transport and secretion at the cell surface. C J C C B C D G E G B The Machinery of Life E F F This image is taken from The Machinery of Life by David S. J Goodsell. It reveals a previously unseen level of F Tour of a Human Cell A I biological scale. Light and electron microscopy may be This illustration simulates what K used to explore the ultrastructure of cells, and X-ray we would see if we could B magnify a portion of a living cell crystallography and NMR spectroscopy may be used to by 1,500,000 times. At this H G magnication, atoms would be B reveal the atomic structure of individual puried about the size of a grain of salt, H cells would be the size of huge molecules, but there is currently no way to observe buildings, and you would be roughly one-fourth the size of the directly the structure of living cells at the molecular level. To purchase this book, visit springer.com earth in height, allowing you to J H walk across the continent in a few I Instead, this illustration is synthesized by combining or your favorite bookseller. E steps. All of the macromolecules Tour of a Human Cell in the cell are shown, including A experimental data on cellular ultrastructure, the atomic proteins, nucleic acids, carbohy- B A This illustration simulates what I drates and lipid bilayers, but all of K the smaller molecules have been we would see if we could structure of molecules, and bioinformatics. A D omitted for clarity. In reality, the magnify a portion of a living cell by 1,500,000 times. At this H empty spaces in this picture are G lled with water, ions, sugars, ATP, magnication, atoms would be B and many other small molecules. about the size of a grain of salt, A H cells would be the size of huge D The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated buildings, and you would be The nucleus is the cell’s library, storing the delicate strandsto the production of of antibodies. The entire process ofare antibody then production processed: is shown, starting cappingfrom enzymes (D) protect one end and polyadenylate roughly one-fourthof the the nucleussize of the through nuclear pore complexes (H). These pores spanI the G With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered Nucleus. the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to earth in height, allowing you to EndoplasmicJ Reticulum. Golgi Apparatus. H Cytoplasm and Cell Membrane. DNA and protecting them from the rigors of the cytoplasm. Muchprocessing of the in the DNA Golgi, and is nishing with transport andpolymerase secretion at the cell surface.(E) adds a repeated string of adenine nucleotides to the other end, walk acrossdouble-layered the continent in a few nuclear membrane and control the tra c of a diverse collection of signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set ofC membrane-bounded sacs stacked like plates. Huge tethering the outside of the membrane. After the vesicle separates from the Golgi, the a railway for delivery of materials. These include thin actin laments (E), thicker steps. All of the macromolecules of sorting and transporting new proteins to their proper destinations. For many J I the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that in the cell are shown, including C A C Tour of a Human Cell B wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate bindingB protein (F). Our DNA proteins, nucleicimportin acids, carbohy proteins- (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally,C the new proteinsD like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteinsA are properly modied and sorted, they are delivered throughout the I clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) drates and lipid bilayers, but all of G and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions the smallermembrane molecules have been is strengthened inside by criss-crossed layers of lamin protein lamentsThis illustration simulates (J). what endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. A D K omitted for clarity. In reality, the we would see if we could E read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is deliveredG out empty spaces in this picture are magnify a portion of a living cell B tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments lled with water, ions, sugars, ATP, by 1,500,000 times. At this H G TM and many other small molecules. magnication, atoms would be with transport proteins (A) that bind to ribosomes and guide new proteins inside as A collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). E B enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real The Machinery of Life F about the size of a grain of salt, D H F This image is taken from The Machinery of Life by David S. The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated cells would be the size of huge G J Goodsell. It reveals a previously unseen level of F to the production of antibodies. The entire process of antibody production is shown, starting from buildings, and you would be A I www.3dmoleculardesigns.com biological scale. Light and electron microscopy may be the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to roughly one-fourth the size of the used to explore the ultrastructure of cells, and X-ray processing in the Golgi, and nishing with transport and secretion at the cell surface. earth in height, allowing you to B C H J J crystallography and NMR spectroscopy may be used to walk across the continent in a few C reveal the atomic structure of individual puried steps. All of the macromolecules I B C molecules, but there is currently no way to observe in the cell are shown, including Tour of a Human Cell A C D B Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 directly the structure of living cells at the molecular level. To purchase this book, visit springer.com proteins, nucleic acids, carbohy- G A I drates and lipid bilayers, but all of Instead, this illustration is synthesized by combining or your favorite bookseller. E This illustration simulates what the smaller molecules have been E K experimental data on cellular ultrastructure, the atomic G A D we would see if we could B omitted for clarity. In reality, the structure of molecules, and bioinformatics. magnify a portion of a living cell empty spaces in this picture are by 1,500,000 times. At this E lled with water, ions, sugars, ATP, H The Machinery of Life magnication, atoms would be F G and many other small molecules. A F B Nucleus. The nucleus is theThis cell’s image library, is taken storing from the The delicate Machinery strands of ofLife by David S. are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporterabout the size nds of anew grain proteins of salt, by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attachedH to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered cells would be the size of huge D J DNA and protecting them fromGoodsell. the rigors It ofreveals the cytoplasm. a previously Much unseen of the level DNA of is polymerase (E) adds a repeated string of adenine nucleotides to the other end, F double-layeredThe narrow nuclear strip membraneis taken from and a plasmacontrol cellthe (showntra c of above), a diverse a cell collection from the of blood that is dedicated of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that buildings, and you would be A wrapped around histone proteinsbiological to form scale. small Light nucleosomes and electron (A) that microscopy compact may be which is then protected by the polyadenylate binding protein (F). Our DNA importinto proteins the production (I), which of carryantibodies. other molecules The entire in process and out. of Theantibody nuclear production is shown, starting from proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place.G the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) roughly one-fourth the size of the I and protect the DNA. When theused DNA to is explore needed, the it is ultrastructure unwrapped, unwound,of cells, and and X-ray must also be edited by large spliceosome complexes (G) to remove intron regions membranethe geneis strengthened in the nucleus, inside proceeding by criss-crossed to synthesis layers in of the lamin endoplasmic protein laments reticulum, (J). continuing to endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to theB next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. earth in height, allowing you to H read by RNA polymerase (B) tocrystallography create a messenger and NMRRNA (C).spectroscopy The RNA molecules may be used to that do not encode proteins. Once the RNA is properly edited, it is delivered out processing in the Golgi, and nishing with transport and secretion at the cell surface. tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the J many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments C reveal the atomic structure of individual puried walk across the continent in a few J ...where molecules become real TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). C enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. molecules, but there is currently no way to observe steps. All of the macromolecules I B C in the cell are shown, including A directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Tour of a Human Cell C D www.3dmoleculardesigns.com B A Instead, this illustration is synthesized by combining or your favorite bookseller. E proteins, nucleic acids, carbohy- G I experimental data on cellular ultrastructure, the atomic drates and lipid bilayers, but all of the smaller molecules have been This illustration simulates what E Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 structure of molecules, and bioinformatics. A D K G omitted for clarity. In reality, the we would see if we could B empty spaces in this picture are magnify a portion of a living cell lled with water, ions, sugars, ATP, by 1,500,000 times. At this H E The Machinery of Life magnication, atoms would be A G Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the and many other small molecules. Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of Fthe new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved withF its function, such as tethered B DNA and protecting them from theThis rigors image of is the taken cytoplasm. from The Much Machinery of the of DNA Life isby David S. polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids.about Thisthe sizesignal of sequencea grain of salt,is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering theD baseH of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that cells would be the size of huge J wrapped around histone proteinsGoodsell. to form Itsmall reveals nucleosomes a previously (A) unseen that compact level of which is then protected by the polyadenylate binding protein (F). Our DNA F importin proteinsThe narrow (I), which strip is carry taken other from molecules a plasma incell and (shown out. The above), nuclear a cell from the blood that is dedicated proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharylA transferase (H). Finally, the new proteins like giantin (A) and GM130I (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNAbiological is needed, scale. it Light is unwrapped, and electron unwound, microscopy and may be must also be edited by large spliceosome complexes (G) to remove intron regions membraneto is the strengthened production inside of antibodies. by criss-crossed The entire layers process of lamin of antibody protein lamentsproduction (J). is shown, starting from endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmicbuildings, reticulum and surface. you would Later, be the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formedI by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids areG cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to createused toa messenger explore the RNA ultrastructure (C). The RNA of moleculescells, and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fullyroughly synthesized one-fourth and safely the size delivered of the inside. Inside, a coat of COPII proteins (I). Any defectiveB proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments Tour of a Human Cell TM earth in height, allowing you to C H crystallography and NMR spectroscopy may be used to processing in the Golgi, and nishing with transport and secretion at the cell surface. with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). J enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real J reveal the atomic structure of individual puried walk across the continent in a few C molecules, but there is currently no way to observe C steps. All of the macromolecules I www.3dmoleculardesigns.com B I in the cell are shown, including A D directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Tour of a Human Cell C Tour of a Human Cell B A SeeThis illustration simulatespage what 14. Instead, this illustration is synthesized by combining or your favorite bookseller. E proteins, nucleic acids, carbohy- G I Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 experimental data on cellular ultrastructure, the atomic drates and lipid bilayers, but all of This illustration simulates what the smaller molecules have been This illustration simulates what E K we would see if we could structure of molecules, and bioinformatics. A D K we would see if we could G omitted for clarity. In reality, the we would see if we could B K magnify a portion of a living cell empty spaces in this picture are magnify a portion of a living cell magnify a portion of a living cell E by 1,500,000 times. At this H lled with water, ions, sugars, ATP, by 1,500,000 times. At this H The Machinery of Life magnication, atoms would be F A G G by 1,500,000 times. At this magnication, atoms would be Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the and many other small molecules. Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry Bthe new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved withF its function, such as tethered B This image is taken from The Machinery of Life by David HS. about the size of a grain of salt, about the size of a grain of salt, H DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering theD baseH of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that J magnication, atoms would be cells would be the size of huge wrapped around histone proteinsGoodsell. to form small It reveals nucleosomes a previously (A) thatunseen compact level of which is then protected by the polyadenylate binding protein (F). Our DNA F importinThe proteins narrow (I), strip which is takencarry otherfrom amolecules plasma cell in (shownand out. above), The nuclear a cell from the blood that is dedicated proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quicklycells recognized would be the by asize signal of huge recognition particle (B) and added to the new proteins by oligosaccharylA transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) G buildings, and you would be and protect the DNA. When the DNAbiological is needed, scale. it Lightis unwrapped, and electron unwound, microscopy and may be must also be edited by large spliceosome complexes (G) to remove intron regions membraneto theis strengthened production of inside antibodies. by criss-crossed The entire layers process of lamin of antibody protein production laments (J). is shown, starting from endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmicbuildings, reticulum and you surface. would Later,be the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formedI by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids areG cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. B about the size of a grain of salt, roughly one-fourth the size of the read by RNA polymerase (B) to createused a to messenger explore the RNA ultrastructure (C). The RNA of molecules cells, and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is roughlyfully synthesized one-fourth and the safely size ofdelivered the inside. Inside, a coat of COPII proteins (I). Any defectiveB proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments earth in height, allowing you to C earth in height, allowing you to TM crystallography and NMR spectroscopy may be used to processing in the Golgi, and nishing with transport and secretion at the cell surface. H H H J ...where molecules become real with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). J J enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. cells would be the size of huge walk across the continent in a few reveal the atomic structure of individual puried I walk across the continent in a few C molecules, but there is currently no way to observe steps. All of the macromolecules steps. All of the macromolecules Tour of a Human Cell www.3dmoleculardesigns.com B C buildings, and you would be in the cell are shown, including directly the structure of living cells at the molecular level. To purchase this book, visit springer.com A in the cell are shown, including A C D Instead, this illustration is synthesized by combining or your favorite bookseller. E B proteins, nucleic acids, carbohy- A B A proteins, nucleic acids, carbohy- G I Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 I This illustration simulates what experimental data on cellular ultrastructure, the atomic drates and lipid bilayers, but all of roughly one-fourth the size of the drates and lipid bilayers, but all of E K the smaller molecules have been we would see if we could structure of molecules, and bioinformatics. the smaller molecules have been A D G A D B earth in height, allowing you to omitted for clarity. In reality, the magnify a portion of a living cell omitted for clarity. In reality, the by 1,500,000 times. At this H empty spaces in this picture are H empty spaces in this picture are J G E lled with water, ions, sugars, ATP, magnication, atoms would be The Machinery of Life lled with water, ions, sugars, ATP, B walk across the continent in a few about the size of a grain of salt, Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding ofF the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteinsA to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered and many other small molecules. A H and many other small molecules. F DNA and protecting them fromThis the image rigors isof taken the cytoplasm. from The Machinery Much of the of LifeDNA by is David S. polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the outside of the membrane. After the vesicle separates from the Golgi, the a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that cells would be the size of huge of sorting and transporting new proteins to their proper destinations. For many D the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules J steps. All of the macromolecules D wrapped around histone proteinsGoodsell. to form It smallreveals nucleosomes a previously (A) unseen that compact level of which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated buildings, and you would be F The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated A and protect the DNA. When thebiological DNA is needed, scale. Light it is unwrapped, and electron unwound, microscopy and may be must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipidsG are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. to the production of antibodies. The entire process of antibody production is shown, starting from roughly one-fourth the size of the G to the production of antibodies. The entire process of antibody production is shown, starting from I in the cell are shown, including I read by RNA polymerase (B) to usedcreate to a explore messenger the ultrastructureRNA (C). The RNA of cells, molecules and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coatA of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to earth in height, allowing you to J the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to B H TM crystallography and NMR spectroscopy may be used to with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. C processing in the Golgi, and nishing with transport and secretion at the cell surface. walk across the continent in a few ...where molecules become real processing in the Golgi, and nishing with transport and secretion at the cell surface. C B A proteins, nucleic acids, carbohy- steps. All of the macromolecules reveal the atomic structure of individual puriedJ J C I C I in the cell are shown, including www.3dmoleculardesigns.com molecules, but there is currently no way to observe A C drates and lipid bilayers, but all of C Tour of a Human Cell B B B proteins, nucleic acids, carbohy- directly the structure of living cells at the molecular level. To purchase this book, visit springer.com C D A I C D E drates and lipid bilayers, but all of G Instead, this illustration is synthesized by combining or your favorite bookseller. G Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 the smaller molecules have been This illustration simulates what the smaller molecules have been experimental data on cellular ultrastructure, the atomic K A D A D we would see if we could E structure of molecules, and bioinformatics. E omitted for clarity. In reality, the G B omitted for clarity. In reality, the G empty spaces in this picture are magnify a portion of a living cell B lled with water, ions, sugars, ATP, by 1,500,000 times. At this H empty spaces in this picture are magnication, atoms would be A E G E The Machinery of Life and many other small molecules. The Machinery of Life F B about the size of a grain of salt, F D Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. WithF so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involvedF with its function, such as tethered lled with water, ions, sugars, ATP, H DNA and protecting them fromThis the image rigors is oftaken the fromcytoplasm. The Machinery Much of ofthe Life DNA by Davidis S. polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that This image is taken from The Machinery of Life by David S. The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated cells would be the size of huge J G wrapped around histone proteinsGoodsell. to form It reveals small nucleosomesa previously unseen (A) that level compact of which is then protected by the polyadenylate binding protein (F). Our DNA F importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added toJ the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) Goodsell. It reveals a previously unseen level of F to the production of antibodies. The entire process of antibody production is shown, starting from buildings, and you would be A I A A and many other small molecules. biological scale. Light and electron microscopy may be the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to roughly one-fourth the size of the and protect the DNA. When thebiological DNA is scale.needed, Light it is and unwrapped, electron microscopyunwound, and may be must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. used to explore the ultrastructure of cells, and X-ray processing in the Golgi, and nishing with transport and secretion at the cell surface. earth in height, allowing you to B J read by RNA polymerase (B) toused create to explore a messenger the ultrastructure RNA (C). The of RNA cells, molecules and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a C coat of COPII proteins (I). AnyB defective proteins are transported out of the H many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments TM J with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. crystallography and NMR spectroscopy may be used to walk across the continent in a few D ...whereC molecules become real crystallography and NMR spectroscopy may be used to reveal the atomic structure of individual puried steps. All of the macromolecules reveal the atomic structure of individual puried I B C The narrow strip is taken from a plasma cell (shown above), a cell from the blood that is dedicated molecules, but there is currently no way to observe in the cell are shown, including Tour of a Human Cell www.3dmoleculardesigns.com molecules, but there is currently no way to observe A C D B directly the structure of living cells at the molecular level. To purchase this book, visit springer.com proteins, nucleic acids, carbohy- G G directly the structure of living cells at the molecular level. To purchase this book, visit springer.com A I to the production of antibodies. The entire process of antibody production is shown, starting from drates and lipid bilayers, but all of Instead, this illustration is synthesized by combining or your favorite bookseller. E Instead, this illustration is synthesized by combining or your favorite bookseller. E I This illustration simulates what Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 the smaller molecules have been E experimental data on cellular ultrastructure, the atomic K experimental data on cellular ultrastructure, the atomic G A D we would see if we could B the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to omitted for clarity. In reality, the structure of molecules, and bioinformatics. structure of molecules, and bioinformatics. magnify a portion of a living cell empty spaces in this picture are by 1,500,000 times. At this E C processing in the Golgi, and nishing with transport and secretion at the cell surface. lled with water, ions, sugars, ATP, H The Machinery of Life magnication, atoms would be F G and many other small molecules. A F B about the size of a grain of salt, J Nucleus. The nucleus is theThis cell’s image library, is taken storing from the The delicate Machinery strands of ofLife by David S. are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attachedH to proteins that need them. For instance, the sugar chains that stabilize leverage neededNucleus. to pinch o The some nucleus of these is the vesicles cell’s library, by forming storing a geodesicthe delicate coat strands on of are then processed:Cytoplasm capping and enzymes Cell (D)Membrane. protect one end The and antibodies polyadenylate make their nal tripof the nucleus athrough network nuclear of laments pore complexes that form a (H). cytoskeleton These pores that span supports the the cell and provides thereEndoplasmic are also some molecules Reticulum. directly involved With so with many its compartments,function, such as our tethered cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered cells would be the size of huge C D J DNA and protecting them fromGoodsell. the rigors It ofreveals the cytoplasm. a previously Much unseen of the level DNA of is polymerase (E) adds a repeated string of adenine nucleotides to the other end, F double-layeredThe narrow nuclear strip membraneis taken from and a plasmacontrol cellthe (showntra c of above), a diverse a cell collection from the of blood that is dedicated of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside ofDNA the membrane.and protecting After them the vesiclefrom the separates rigors of from the cytoplasm.the Golgi, the Much of the DNA is polymerasethrough (E) adds the a repeatedcytoplasm string to the of cell adenine membrane, nucleotides pulled to by the kinesin other (A)end, along microtubulesdouble-layered a nuclearrailway formembrane delivery andof materials. control the These tra c include of a diverse thin actin collection laments of (E), thicker antibodiesof sorting (G) used and transportingto recognize bacterianew proteins and viruses, to their the proper IL-4 destinations.receptor (H) that For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that buildings, and you would be A wrapped around histone proteinsbiological to form scale. small Light nucleosomes and electron (A) that microscopy compact may be which is then protected by the polyadenylate binding protein (F). Our DNA importinto proteins the production (I), which of carryantibodies. other molecules The entire in process and out. of Theantibody nuclear production is shown, starting from proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place.G the proteins are properly modied and sorted, they are delivered throughout the clathrin coat fallswrapped o and around the vesicle histone is guided proteins to to its form ultimate small destination. nucleosomes (A) that compact which is then(B). Longprotected tethering by the proteins polyadenylate like golgin binding (C) help protein the vesicle (F). Our nd DNA its proper destination.importin proteinsintermediate (I), which carrylaments other (F), molecules and huge in microtubules. and out. The nuclearThe cell membrane is studded receivesproteins, messages such from as the other antibodies cells in madethe immune by this system,plasma andcell, SNAREthe journey proteins starts (I) with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) C roughly one-fourth the size of the I B and protect the DNA. When theused DNA to is explore needed, the it is ultrastructure unwrapped, unwound,of cells, and and X-ray must also be edited by large spliceosome complexes (G) to remove intron regions membranethe geneis strengthened in the nucleus, inside proceeding by criss-crossed to synthesis layers in of the lamin endoplasmic protein laments reticulum, (J). continuing to endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to theB next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also Thebe edited cytoplasm by large of our spliceosome cells is lled complexes with enzymes (G) to and remove other intron proteins regions performing theirmembrane is strengthenedwith a diverse inside collection by criss-crossed of proteins, layersmany of laminwhich protein have polysaccharide laments (J). groups and theendoplasmic exocyst complex reticulum. (J) that The assistendoplasmic the docking reticulum and fusion is an interconnectedof transport vesicles. series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. earth in height, allowing you to D H read by RNA polymerase (B) tocrystallography create a messenger and NMRRNA (C).spectroscopy The RNA molecules may be used to that do not encode proteins. Once the RNA is properly edited, it is delivered out processing in the Golgi, and nishing with transport and secretion at the cell surface. tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the J read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do notmany encode tasks. proteins. These include Once the ribosomes RNA is properly (D) and edited, the other it is machinery delivered outof protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On thetubules inside and of the sacs. membrane, The membrane a tough surrounding network of the spectrin endoplasmic (K) and actinrecticulum laments is lled o when the protein is fully synthesized and safely delivered inside. Inside, a C coat of COPII proteins (I). Any defective proteins are transported out of the C many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments walk across the continent in a few TM TM reveal the atomic structure of individual puried with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). J the membrane and in communication across the membrane. In this plasma cell, formswith a sturdy transport infrastructure proteins (A)that that supports bind to the ribosomes delicate membrane.and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real ...whereC molecules become real enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with molecules, but there is currently no way to observe steps. All of the macromoleculesG I B C in the cell are shown, including A directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Tour of a Human Cell www.3dmoleculardesigns.com C D www.3dmoleculardesigns.com B A Instead, this illustration is synthesized by combining or your favorite bookseller. E proteins, nucleic acids, carbohy- G I drates and lipid bilayers, but all of experimental data on cellular ultrastructure, the atomic E Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 the smaller molecules have been This illustration simulates what E Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 structure of molecules, and bioinformatics. A D K G G B omitted for clarity. In reality, the we would see if we could B empty spaces in this picture are magnify a portion of a living cell lled with water, ions, sugars, ATP, by 1,500,000 times. At this H E The Machinery of Life magnication, atoms would be A G Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the and many other small molecules. Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of Fthe new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved withF its function, such as tethered B DNA and protecting them from theThis rigors image of is the taken cytoplasm. from The Much Machinery of the of DNA Life isby David S. polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids.about Thisthe sizesignal of sequencea grain of salt,is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering theD baseH of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that E cells would be the size of huge J The Machinery of Life wrapped around histone proteinsGoodsell. to form Itsmall reveals nucleosomes a previously (A) unseen that compact level of which is then protected by the polyadenylate binding protein (F). Our DNA F importin proteinsThe narrow (I), which strip is carry taken other from molecules a plasma incell and (shown out. The above), nuclear a cell from the blood that is dedicated proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharylA transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNAbiological is needed, scale. it Light is unwrapped, and electron unwound, microscopy and may be must also be edited by large spliceosome complexes (G) to remove intron regions membraneto is the strengthened production inside of antibodies. by criss-crossed The entire layers process of lamin of antibody protein lamentsproduction (J). is shown, starting from endoplasmic reticulum. The endoplasmic reticulumF is an interconnected series of delivered to the endoplasmicbuildings, reticulum and surface. you would Later, be the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formedI by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids areG cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to createused toa messenger explore the RNA ultrastructure (C). The RNA of moleculescells, and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fullyroughly synthesized one-fourth and safely the size delivered of the inside. Inside, a coat of COPII proteins (I). Any defectiveB proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments F earth in height, allowing you to C H TM crystallography and NMR spectroscopy may be used to processing in the Golgi, and nishing with transport and secretion at the cell surface. with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). J enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. This image is taken from The Machinery of Life by David S. ...where molecules become real J reveal the atomic structure of individual puried walk across the continent in a few C J Goodsell. It reveals a previously unseen level of molecules, but there is currently no way to observe C steps. All of the macromolecules I F www.3dmoleculardesigns.com B in the cell are shown, including A D directly the structure of living cells at the molecular level. To purchase this book, visit springer.com A Tour of a Human Cell C proteins, nucleic acids, carbohy- B A biological scale. Light and electron microscopy may be Instead, this illustration is synthesized by combining or your favorite bookseller. E G Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 I experimental data on cellular ultrastructure, the atomic drates and lipid bilayers, but all of the smaller molecules have been This illustration simulates what E used to explore the ultrastructure of cells, and X-ray structure of molecules, and bioinformatics. A D K B G omitted for clarity. In reality, the we would see if we could B crystallography and NMR spectroscopy may be used to empty spaces in this picture are magnify a portion of a living cell lled with water, ions, sugars, ATP, by 1,500,000 times. At this H E The Machinery of Life F A G Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the and many other small molecules. Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. Themagnication, transporter atomsnds new would proteins be by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved withF its function, such as tethered B reveal the atomic structure of individual puried This image is taken from The Machinery of Life by David S. about the size of a grain of salt, DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering theD baseH of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that J molecules, but there is currently no way to observe wrapped around histone proteinsGoodsell. to form small It reveals nucleosomes a previously (A) thatunseen compact level of which is then protected by the polyadenylate binding protein (F). Our DNA F importinThe proteins narrow (I), strip which is takencarry otherfrom amolecules plasma cell in (shownand out. above), The nuclear a cell from the blood that is dedicated proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quicklycells recognized would be the by asize signal of huge recognition particle (B) and added to the new proteins by oligosaccharylA transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNAbiological is needed, scale. it Lightis unwrapped, and electron unwound, microscopy and may be must also be edited by large spliceosome complexes (G) to remove intron regions membraneto theis strengthened production of inside antibodies. by criss-crossed The entire layers process of lamin of antibody protein production laments (J). is shown, starting from endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmicbuildings, reticulum and you surface. would Later,be the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formedI by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids areG cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to createused a to messenger explore the RNA ultrastructure (C). The RNA of molecules cells, and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is roughlyfully synthesized one-fourth and the safely size ofdelivered the inside. Inside, a coat of COPII proteins (I). Any defectiveB proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments directly the structure of living cells at the molecular level. To purchase this book, visit springer.com earth in height, allowing you to C TM crystallography and NMR spectroscopy may be used to processing in the Golgi, and nishing with transport and secretion at the cell surface. with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. H ...where molecules become real J J enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with reveal the atomic structure of individual puried walk across the continent in a few C Instead, this illustration is synthesized by combining or your favorite bookseller. E molecules, but there is currently no way to observe steps. All of the macromolecules www.3dmoleculardesigns.com B C directly the structure of living cells at the molecular level. To purchase this book, visit springer.com in the cell are shown, including A C D experimental data on cellular ultrastructure, the atomic Instead, this illustration is synthesized by combining or your favorite bookseller. E proteins, nucleic acids, carbohy- B A G Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 I experimental data on cellular ultrastructure, the atomic drates and lipid bilayers, but all of structure of molecules, and bioinformatics. the smaller molecules have been E structure of molecules, and bioinformatics. G A D B omitted for clarity. In reality, the empty spaces in this picture are E The Machinery of Life lled with water, ions, sugars, ATP, F Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span andthe many other small molecules. Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteinsA to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involvedF with its function, such as tethered DNA and protecting them fromThis the image rigors isof taken the cytoplasm. from The Machinery Much of the of LifeDNA by is David S. polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering D through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules J wrapped around histone proteinsGoodsell. to form It smallreveals nucleosomes a previously (A) unseen that compact level of which is then protected by the polyadenylate binding protein (F). Our DNA F importinThe narrow proteins strip (I), iswhich taken carry from other a plasma molecules cell (shown in and above), out. The a cellnuclear from the blood that is dedicated proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharylA transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cellsand protect need the DNA. ways When thebiological DNA is needed, scale.they Light it is unwrapped, and are electron being unwound, microscopy made.and may be Themust transporteralso be edited by large spliceosomends new complexes proteins (G) to remove byintron looking regions formembraneto a the special production is strengthened of antibodies. inside by The criss-crossed entire process layersisomerase of of antibody lamin protein production (E) laments and is shown, (J). cyclophilin starting from (F)endoplasmic assist reticulum. in the The foldingendoplasmic reticulum of the is an new interconnected proteins. series of Polysaccharidedelivered to the endoplasmic reticulum surface. Later, the signal Golgisequence is clipped Apparatus.proteins are transported The to the transport next step in small vesiclestransport vesicles, carry Iformed bythe a new proteinsThe to Golgi the is the processing and sortingattached plant of the cell. to Sugars proteins and lipidsG are that needcell in small them. transport Forvesicles. instance, The protein clathrin the (C) provides sugar the molecularchains that stabilize leverage needed to pinch o some of theseThe cytoplasm vesicles of our cells by is lled forming with enzymes anda geodesic other proteins performing coat their on with a diverse collection of proteins, many of which haveCytoplasm polysaccharide groups andand the exocystCell complex Membrane. (J) that assist the docking and The fusion ofantibodies transport vesicles. make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered read by RNA polymerase (B) to usedcreate to a explore messenger the ultrastructureRNA (C). The RNA of cells, molecules and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out the gene in the nucleus, proceeding to synthesis in the endoplasmic reticulum, continuing to tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defectiveB proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. 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This signal sequence is the rst thing madeprocessing by in the the Golgi, and nishing with transportchains and secretion are at made the cell surface. by a series of enzymeswith transport proteins in the (A) that membrane bind to ribosomes and (G) guide and new proteins nally inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After theenzymes vesicle of glycolysis, separates and other synthetic from enzymes. the TheGolgi, cytoplasm the is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering J through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules reveal the atomic structure of individual puried C wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such aswww.3dmolecula the antibodiesrdesigns.com made by this plasma cell, the journey starts with the molecules, butribosome, there is currently no andway to observe it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally,C the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) directly the structure of living cells at the molecular level. To purchase this book, visit springer.com B C D E and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of Instead, this illustrationdelivered is synthesized to by the combining endoplasmic or your favorite reticulum bookseller. surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transportG vesicles. The protein clathrin (C) provides the molecular The cytoplasmCopyright of our 3D Molecular cells Designsis lled - All Rights with Reserved enzymes - 2009, 2016, 2018and otherVersion 1.2 -proteins 8/2018 performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics. E read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of theG B many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real The Machinery of Life E Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the foldingF of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involvedF with its function, such as tethered DNA and protecting them fromThis the image rigors is oftaken the fromcytoplasm. The Machinery Much of ofthe Life DNA by Davidis S. polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that J wrapped around histone proteinsGoodsell. to form It reveals small nucleosomesa previously unseen (A) that level compact of which is then protected by the polyadenylate binding protein (F). Our DNA F importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharylA transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) www.3dmoleculardesigns.com and protect the DNA. When thebiological DNA is scale.needed, Light it is and unwrapped, electron microscopyunwound, and may be must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) toused create to explore a messenger the ultrastructure RNA (C). The of RNA cells, molecules and X-ray that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). AnyB defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments www.3dmoleculardesigns.comTM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane. ...where molecules become real crystallography and NMR spectroscopy may be used to enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with reveal the atomic structure of individual puried www.3dmoleculardesigns.com molecules, but there is currently no way to observe Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 directly the structure of living cells at the molecular level. To purchase this book, visit springer.com Instead, this illustration is synthesized by combining or your favorite bookseller. E Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016, 2018 Version 1.2 - 8/2018 experimental data on cellular ultrastructure, the atomic structure of molecules, and bioinformatics.

Nucleus. The nucleus is the cell’s library, storing the delicate strands of are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the Endoplasmic Reticulum. With so many compartments, our cells need ways they are being made. The transporter nds new proteins by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide Golgi Apparatus. The transport vesicles carry the new proteins to the attached to proteins that need them. For instance, the sugar chains that stabilize leverage needed to pinch o some of these vesicles by forming a geodesic coat on Cytoplasm and Cell Membrane. The antibodies make their nal trip a network of laments that form a cytoskeleton that supports the cell and provides there are also some molecules directly involved with its function, such as tethered DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) adds a repeated string of adenine nucleotides to the other end, double-layered nuclear membrane and control the tra c of a diverse collection of of sorting and transporting new proteins to their proper destinations. For many signal sequence of amino acids. This signal sequence is the rst thing made by the chains are made by a series of enzymes in the membrane (G) and nally Golgi, a set of membrane-bounded sacs stacked like plates. Huge tethering the base of the Y-shaped antibody are trimmed and perfected in the Golgi. When the outside of the membrane. After the vesicle separates from the Golgi, the through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules a railway for delivery of materials. These include thin actin laments (E), thicker antibodies (G) used to recognize bacteria and viruses, the IL-4 receptor (H) that wrapped around histone proteins to form small nucleosomes (A) that compact which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear proteins, such as the antibodies made by this plasma cell, the journey starts with the ribosome, and it is quickly recognized by a signal recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new proteins like giantin (A) and GM130 (B) guide the vesicles to the right place. the proteins are properly modied and sorted, they are delivered throughout the clathrin coat falls o and the vesicle is guided to its ultimate destination. (B). Long tethering proteins like golgin (C) help the vesicle nd its proper destination. intermediate laments (F), and huge microtubules. The cell membrane is studded receives messages from other cells in the immune system, and SNARE proteins (I) and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and must also be edited by large spliceosome complexes (G) to remove intron regions membrane is strengthened inside by criss-crossed layers of lamin protein laments (J). endoplasmic reticulum. The endoplasmic reticulum is an interconnected series of delivered to the endoplasmic reticulum surface. Later, the signal sequence is clipped proteins are transported to the next step in small transport vesicles, formed by a The Golgi is the processing and sorting plant of the cell. Sugars and lipids are cell in small transport vesicles. The protein clathrin (C) provides the molecular The cytoplasm of our cells is lled with enzymes and other proteins performing their with a diverse collection of proteins, many of which have polysaccharide groups and the exocyst complex (J) that assist the docking and fusion of transport vesicles. read by RNA polymerase (B) to create a messenger RNA (C). The RNA molecules that do not encode proteins. Once the RNA is properly edited, it is delivered out tubules and sacs. The membrane surrounding the endoplasmic recticulum is lled o when the protein is fully synthesized and safely delivered inside. Inside, a coat of COPII proteins (I). Any defective proteins are transported out of the many tasks. These include ribosomes (D) and the other machinery of protein synthesis, attached on the outer side. Many of these are involved in tra c of molecules across On the inside of the membrane, a tough network of spectrin (K) and actin laments ...where molecules become real TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as collection of chaperonins such as BiP (C), Grp94 (D), calnexin and protein disulde endoplasmic reticulum and destroyed by the proteasome (J). enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with the membrane and in communication across the membrane. In this plasma cell, forms a sturdy infrastructure that supports the delicate membrane.

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