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Flu Fight: Immunity & Infection Panorama© Page 15

NEW Durable Plastic! Synapse Construction Kit© Page 19 Antibody and Antigen Models Page 17 Insulin Model Page 9 Our Customers’ Favorite Products

Water Kit© Page 3 Flow of Genetic Information Kit© Page 13 DNA Discovery Kit© Page 11

Enzymes in Action Kit© Page 8 Amino Acid Starter Kit© Page 7 Phospholipid & Membrane Transport Kit© Page 5

David Goodsell Cellular Landscapes Page 14

3dmoleculardesigns.com Made in the U.S.A. ...where molecules become real TM

2018 Product by Category

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

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 ...... 23 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 © Synapse Poster ...... 14 - 15

3D Molecular Designs utilizes magnets in many products to help students understand the inter- and intra-molecular forces in the molecular world. In compliance with the Consumer Product Safety Improvement Act of 2008, 3DMD adds the warnings below to our products and encourages the safe use of our products in classrooms and other science education settings. Please contact us if you have 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.

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 magnetized to reflect their positive or negative charges (except for non-polar

ethane). Lessons and activities are available online. 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), Phospholipid & Membrane Transport Kit© (page 5) and Water Tattoos (page 21).

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS © CAUTION: Science Education Product See our Phospholipid & Membrane Transport Kit (page 5)! Please see bottom of page 2 for details.

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) and the 3x3x3 lattice contains 27 ions (13 of 1 type of ion and 14 of the other). Lattices do not include 3DMD water molecules. Water molecules are sold in Water Kits© (see above). 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 Please see bottom of page 2 for details.

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

2018 Channel Protein Mini Models Sodium Channel Mini Model

Sodium Channel Channel Sodium This model of a bacterial sodium channel shows the pore domain of the protein. The pore

Mini Model Mini 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. Voltage-gated sodium channels play a critical role in generating the action potential in signaling neurons. As they open — in response to a stimulus — sodium ions enter the cell, leading to depolarization and a propagation of the action potential. 3.75” Plaster Model $101 (SCMM) Also see Water Kit© and NaCl Lattice© (page 3).

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 are strategically positioned near the center of the hourglass l and provide selectivity to this channel, allowing only water molecules pass through. 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 passage through the channel. Potassium Channel Mini Model Potassium Channel

The potassium channel is a 4-subunit, transmembrane protein that allows the rapid passage of Mini Model Mini potassium ions — but not sodium ions — across the membrane. The protein backbones of the 4 subunits come together to 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). 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. The model also displays additional amino acid side chains that are important in stabilizing the interaction between these 2 proteins. 5” Plaster Model $145 (PCSMM)

Channel protein mini models are built at the same scale.

4 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

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, a micelle and a 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. Transport 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 Please see bottom of page 2 for details.

Phosphorylated Na+/K+ Pump Phospholipid Structure

Phospholipid Modeling Set

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: phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine and sphingomyelin, 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©. Indicates Phospholipid Phospholipid Modeling Set $599 (PLMS-01) • Phosphatidylcholine $121 (PLMS-A) Double Bond Modeling Set Phosphatidylserine $116 (PLMS-B) • Phosphatidylinositol $126 (PLMS-C) Phosphatidylethanolamine $113 (PLMS-D) • Sphingomyelin $125 (PLMS-E)

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

2018 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 mutation 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. Teacher notes and student handouts are available online. The folding kit can be used successfully by 6 to 9 students working in 3 teams. © Folding Kit $118 (BGFK) • Prefolded $120 (BGM)

© It’s best if your students first use the Amino Acid Starter Kit (page 7) before using the ! WARNING: CHOKING HAZARD β-Globin Folding Kit©. Also see Map of the Human β-Globin Gene© (below). The prefolded model can β © CAUTION: Science Education Product be used as a same-scale model when using the -Globin Folding Kit or to teach concepts noted above. Please see bottom of page 2 for details.

β-Globin Mini Models

β-Globin Mini Models Mini β-Globin β-globin, a small protein (146 amino acids), transports oxygen throughout our bodies. Our 2 β-Globin Mini Models feature 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 model on the left can be used as an accurate, smaller-scale template when using the β-Globin Folding Kit© (above). The 3 colors correspond to the 3 fragments in the β-Globin Folding Kit©. Side chains on the model to the right indicate mutations that are noted on the Teacher Map of the Human β-Globin Gene© (below). The 3 colors of the alpha carbon backbone correspond to the 3 exons in the gene. 4” Plaster Model $92 (BGMMFK) 4” Plaster Model $92 (BGMMPBI)

Use with β-Globin Folding Kit© Also see β-Globin Folding Kit© (above) and Teacher Map of the Human β-Globin Gene© (below). Use with Map of the Map of the Human β-Globin Gene© Human β-Globin Gene©

Don’t just tell your students about triplet codons, reading frames or introns and exons. Let them Map of the Human of the Human Map discover these eukaryotic gene features as they explore the Map of the Human β-Globin Gene©. β-Globin Gene β-Globin Starting with the protein sequence, students work backward to discover the β-globin gene. AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATTTAAATTATTTCTGAATATTT A 3DMD Paper BioInformatics Activity© 62000 62050 Student maps can be used62100 by individuals or small groups and62150 are available in sets of 1, 3 or 12. 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 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+--- 63773

β-Globin mRNA © TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTATTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATTCAGGTTGATGATTTGACCCCCTATAATACTTCCCGGAACTCGTAGACCTAAGACGGATTATTTTTTGTAAATAAAAGTAACGTTACTACATAAATTTAATAAAGACTTATAAA -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). Map of the β-Globin Gene AGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTATTGCTT ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAATATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAA 62000 62050 62100 62150 62200 62206 62250 62265 62279 62283 62300 62350 62388 62400 62450 61981 ------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+------+

Version 2.4 Version One teacher’s map comes with every combo. The teacher’s TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTATTTTCAGTCCCGTCTCGGTAGATAACGAA TGTAAACGAAGACTGTGTTGACACAAGTGATCGTTGGAGTTTGTCTGTGGTACCACGTGGACTGAGGACTCCTCTTCAGACGGCAATGACGGGACACCCCGTTCCACTTGCACCTACTTCAACCACCACTCCGGGACCCGTCCAACCATAGTTCCAATGTTCTGTCCAAATTCCTCTGGTTATCTTTGACCCGTACACCTCTGTCTCTTCTGAGAACCCAAAGACTATCCGTGACTGAGAGAGACGGATAACCAGATAAAAGGGTGGGAATCCGACGACCACCAGATGGGAACCTGGGTCTCCAAGAAACTCAGGAAACCCCTAGACAGGTGAGGACTACGACAATACCCGTTGGGATTCCACTTCCGAGTACCGTTCTTTCACGAGCCACGGAAATCACTACCGGACCGAGTGGACCTGTTGGAGTTCCCGTGGAAACGGTGTGACTCACTCGACGTGACACTGTTCGACGTGCACCTAGGACTCTTGAAGTCCCACTCAGATACCCTGGGAACTACAAAAGAAAGGGGAAGAAAAGATACCAATTCAAGTACAGTATCCTTCCCCTCTTCATTGTCCCATGTCAAATCTTACCCTTTGTCTGCTTACTAACGTAGTCACACCTTCAGAGTCCTAGCAAAATCAAAGAAAATAAACGACAAGTATTGTTAACAAAAGAAAACAAATTAAGAACGAAAGAAAAAAAAAGAAGAGGCGTTAAAAATGATAATATGAATTACGGAATTGTAACACATATTGTTTTCCTTTATAGAGACTCTATGTAATTCATTGAATTTTTTTTTGAAATGTGTCAGACGGATCATGTAATGATAAACCTTATATACACACGAATAAACGTATAAGTATTAGAGGGATGAAATAAAAGAAAATAAAAATTAACTATGTATTAGTAATATGTATAAATACCCAATTTCACATTACAAAATTATACACATGTGTATAACTGGTTTAGTCCCATTAAAACGTAAACATTAAAATTTTTTACGAAAGAAGAAAATTATATGAAAAAACAAATAGAATAAAGATTATGAAAGGGATTAGAGAAAGAAAGTCCCGTTATTACTATGTTACATAGTACGGAGAAACGTGGTAAGATTTCTTATTGTCACTATTAAAGACCCAATTCCGTTATCGTTATAAAGACGTATATTTATAAAGACGTATATTTAACATTGACTACATTCTCCAAAGTATAACGATTATCGTCGATGTTAGGTCGATGGTAAGACGAAAATAAAATACCAACCCTATTCCGACCTAATAAGACTCAGGTTCGATCCGGGAAAACGATTAGTACAAGTATGGAGAATAGAAGGAGGGTGTCGAGGACCCGTTGCACGACCAGACACACGACCGGGTAGTGAAACCGTTTCTTAAGTGGGGTGGTCACGTCCGACGGATAGTCTTTCACCACCGACCACACCGATTACGGGACCGGGTGTTCATAGTGATTCGAGCGAAAGAACGACAGGTTAAAGATAATTTCCAAGGAAACAAGGGATT 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 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 PDonor SpliceW Site A G W Y Q G Y K T G INTRONL RI R P I E T Acceptor G Splice H Site 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 R F F E S F G D L S T 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 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 Student Copy Student 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 Globin Gene Map Copyright 2013 3D Molecular Designs, LLC 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 reading Qb A LS A RC R A S K D RL Y G A C H TH L DS L T NL W SR H T H L G LH A N G L L AP G A P G R DA G AS R A *G H KG S Q E G R AV I Y C C L RH L L Y L T CQ L CP S L VA T SG N R Q H H G A P E D S R* G EG V C *R Y CS P V W G Q GW E R * G * GS W W P * G GP G QQ V G V I K VG T R I Q V K* G D V Q * TK L GR M W QR Q RV R L * L G FG * * D A L QT L S* A Y KW S IL F P G P L GM C W W W S RT L G Q P R RG S LR S P LL G IL C P G L L MF L L * W A *T L RA * R LL M AT R K L C S VS P L A V M YA W L W T W ST T SI R A F P L P H * P V S LC T V G T S CC T WW I L WR T S G * T V Y GL T L G D V PF F PR L L GF Y GS * V L H V IS G R P G E LV T G G Y S IL E WC E T PD E *L L H L Q C MG S L L R I LV L VW S F AI C CT S * L Q L FR S F * V * RF L L L S F MF F FA S A R I F TK I I C L N SA L T V L C PI T KL G N VI S EM I H A * V WT * K L K T TL H SW L P TS T LT L F S G I YR V C A L F PA Y S L * S PP Y FH I F * F Y FV * L S I H CN H Y T T Y VL W VT K V S* C FC N M T C T HW I D I Q I LR V IR L H TL * FS * K G M L S* S F V N I YL F C G L S TY F *L Y F D P * SV L S F F R FA I M P I Q LC I ML P L FC T IY L K G N N S* D N V F W HV K AV I A II F LG H I R N I SG A Y E K L V* L M T * E GV S YY C * S * Q L Q S E S Y WH S A E F I TL W LD G * EG W I* I L L S P SH * A Q L L CL I M G F I SP L IL F L RP Q LI L G V N V L V C V V L SA H HF F G IK E FC T P C P V QS A A * Y Q QK V V L A G FV A NS A L F A H KV Y H * * A FR F L L A V LQ F LS L K FV P LF 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 - map features highlighted reading frames and mutation frames TM www.3dmoleculardesigns.com 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

β Consensus ...where molecules become real Consensus Consensus EXON INTRON INTRON EXON 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 CV H L T PTATA BoxE TATAE A A TK S A V T A The Lfirst methionine W amino G acid is K V N V D E V G G E A L G R L Note: V all introns S begin withR and endL with Q DonorD Splice R Site F K E AcceptorT Splice N Site 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 * CAAT Box GG( )CAATCT ( T ) (A ) cleaved from the β-Globin protein This negatively charged GU AG. Promoter Region T V C A soon after its synthesis. glutamic acid (E) is AG GU YYYYYYYYYNCAG G sites. Teachers’ notes, instructions and student handout are replaced by a hydrophobic valine (V) in sickle cell anemia. A G

The GU preceding this mutation becomes a new donor splice site that is used 40% of the time (β+ thalassemia). provided online. All maps are laminated. 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 Mutations Creates a new acceptor splice site; adds 19 nucleotides to mRNA and results in frameshift (β thalassemia). Hemoglobin Hiroshima begins 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 1 Student and 1 Teacher Map Combo $40 (BGGM-01S-01T) 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 3 Student and 1 Teacher62100 Map Combo $60 (BGGM-03S-01T) 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 TCGGTCACGGTCTTCTCGGTTCCTGTCCATGCCGACAGTAGTGAATCTGGAGTGGGACACCTCGGTGTGGGATCCCAACCGGTTAGATGAGGGTCCTCGTCCCTCCCGTCCTCGGTCCCGACCCGTA12 Student and 1 Teacher Map ComboTTTTCAGTCCCGTCTCGGTAGATAACGAA $145 (BGGM-12S-01T) 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 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 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 6 Models are made of plaster by 3-D printing and should be handled with care. Models will break if dropped, held tightlyT or handled roughly. 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

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 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 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

+ 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

- 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©

Your students will explore the primary, secondary and tertiary structure of proteins with this captivating kit. They will learn the chemical properties of the 20 amino acid side chains through a dual coloring scheme — a colored clip at the base of each side chain indicates chemical properties while embedded colored balls in side chain models show atomic structure. Understanding protein structure begins with this © unique combination of atomic and chemical properties of the amino acids. Through 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 with additional folding activities.

Each 1-group set includes 1 chemical properties circle, 1 amino acid side chain list, 22 amino acids, 1 4-foot mini toober, 15 plastic clips and 6 hydrogen bond connectors. Multiply each item by 3, 5 or 6 for the 3-group, 5-group and 6-group sets. Teacher notes, student handouts and interactive Jmol visualization tools are available online. ! CHOKING HAZARD WARNING: Starter Kit Acid Amino © © CAUTION: Science Education Product Project Lead the Way selected the Amino Acid Starter Kit for its BioMedical Sciences™ Program. Please see bottom of page 2 for details. 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), Tour of a Human Cell©, Mitochondria Poster©, E. Coli Poster© and Neuromuscular Synapse Poster© (page 15), Amino Acid Starter Kit Poster© (below) and Genetic Codon Posters© (page 23).

Tertiary Structure Secondary Structure Active Site

Amino Acid Starter Kit Poster©

The Amino Acid Starter Kit Poster© allows students to connect the chemical structure of each amino acid side chain — as it is commonly represented in textbooks — with the physical models of each side chain supplied in the Amino Acid Starter Kit©. The poster features a dual color scheme. First, each atom of © the side chain is color-coded according to atom type (red for oxygen, blue for nitrogen, gray for carbon and yellow for sulfur). Second, the base of each side chain is color-coded to reflect the overall chemical property of the side chain (yellow for hydrophobic side chains, red for acidic side chains, blue for basic side Kit Poster chains, white for hydrophilic but uncharged side chains and green for cysteines). © Amino Acid Starter Kit Poster $24 (AASKP) Starter Acid Amino Also see Amino Acid Starter Kit© (above) and Genetic Codon Posters© (page 23).

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

2018 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. Multiply each item by 3, 6 or 12 for the 3-group, 6-group and 12-group sets. Teacher notes and student handouts are available online. ! WARNING: CHOKING HAZARD © 12-Group Set $121 (EAK-12) • 6-Group Set $62 (EAK-06) • 3-Group Set $35 (EAK-03) Science Education Product © CAUTION: 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 will:

• 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 potentially have a significant impact on substrate binding in the active site. ! WARNING: CHOKING HAZARD © ! WARNING: SMALL MAGNETS Lessons and activities are available online. Science Education Product CAUTION: © Please see bottom of page 2 for details. Substrate Specificity Kit $38 (SSK-01) Also see Enzymes in Action Kit (above).

Acetylcholinesterase Active Site Cube©

Now your students can unfold an enzyme to see how the precisely Acetylcholinesterase positioned active site amino acids bind to specific substrates to catalyze a Active Site Cube 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. This has led to the emergence of insecticide-resistant mosquitoes. The substrate, insecticide and mutant His 480 Glu 367 amino acid side chain bind to the enzyme with magnets.

© Ser 238 Acetylcholine Insecticide A mutant 5” Plaster Cube Model $950 (ACHASC-5) (substrate) side chain 3” Plaster Cube Model $499 (ACHASC-3) Not eligible for discounts ! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product 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. Multiply each item by 3 or 6 for the 3-group and 6-group sets (each set also includes 1 teacher mRNA map). Teacher notes, student handouts and interactive Jmol visualization tools are available online. 6-Group Set $260 (INSFK-06) 3-Group Set $140 (INSFK-03) 1-Group Set $54 (INSFK-01)

It’s best if your students first use the Amino Acid Kit Protein Insulin mRNA to 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 23). Insulin Model – NEW Durable Plastic!

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 peptide with a longer B chain (colored orange) composed of an alpha helix and a beta strand, and a shorter A chain (colored 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.

Insulin Poster©

By using the insulin protein as a starting point, teachers can weave together © a broad range of biology topics including the flow of genetic information, biochemistry and protein structure, cellular organelles, anatomy, physiology and cell biology of glucose homeostasis, energy metabolism, the endocrine and digestive systems, recombinant DNA technologies and new approaches to monitor blood glucose levels and control diabetes.

Insulin Poster $21 (INSP) Also see Insulin mRNA to Protein Kit© (above). Insulin Poster

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

2018 Hemoglobin Nylon Model Nylon Model Hemoglobin If you could have only one model with which to teach proteins, this is it — a 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. WARNING: CHOKING HAZARD 6.5” Hemoglobin $750 (NHGM) Not eligible for discounts ! WARNING: SMALL MAGNETS CAUTION: Science Education Product Please see bottom of page 2 for details. Hemoglobin Poster©

Hemoglobin Hemoglobin From exploring the question, “Why do we breathe?” to illustrating the structure of

Poster hemoglobin, the cause of sickle cell anemia and the physiology of oxygen transport, our colorful Hemoglobin Poster© will spark new inquiry among your students. Best used as a companion guide for 3DMD’s Hemoglobin Nylon Model (above), ß-Globin Folding © ©

© Kit , Map of the Human ß-Globin Gene and ß-Globin Mini Models (page 6), the poster can also stand alone to help facilitate meaningful discussions about hemoglobin. Hemoglobin Poster© (21” x 22”) $21 (HGP)

DNA Mini Model DNA Mini Model DNA Mini This model immediately engages your students in thinking about the structure of DNA. You can guide a discussion of the nature of models — and the usefulness of multiple representations of any molecular structure. The DNA Mini Model represents the classic DNA double helix in 4 formats. The bottom section of the model shows a surface format emphasizing major and minor grooves. Moving up, all atoms are in a CPK colored spacefilled format. The next section shows the 4 nitrogenous bases in a CPK wireframe format. In the top section of the model, each of the 4 bases is colored with a solid color. 8” Plaster Model with Base $178 (DNA4FMM)

CRISPR/Cas9 Mini Model

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 CRISPR/Cas9 CRISPR/Cas9

Mini Model Mini Cas9 component of the CRISPR gene editing 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: SMALL MAGNETS 5” Plaster Model $246 (CC9MM) • 11” Nylon Model $1,450 (NCC9M) Please see bottom of page 2 for details. Not eligible for discounts

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

DNA Discovery Kit©

Let your students discover the structure of DNA — just as Watson and Crick did. The DNA Discovery Kit© combines magnets with accurate 3-D nucleotides which make the © kit self-instructive. As your students discover A-T and G-C base pairs, they will feel the hydrogen bonding. Teacher-developed and field-tested, the 12 Base Pair Set contains 6 A-T and 6 G-C base pairs, display stand and 2 mini toobers. Extensive activities, materials and background information are available online. The 2 Base Pair Set includes 1 A-T and 1 G-C base pair.

Project Lead the Way© selected the DNA Discovery Kit© for its BioMedical Sciences™ Program.

12 Base Pairs (Classroom Set) $299 (DNA-12) Kit DNA Discovery 2 Base Pairs (A-T and G-C) $52 (DNA-02)

Also see Nucleosome, Ribosome and tRNA Mini Models (page 16), Tour of a Human Cell© (page 15) and Adenosine Triphosphate (ATP) Mini Model (page 14).

! WARNING: CHOKING HAZARD ! WARNING: SMALL MAGNETS CAUTION: Science Education Product 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 © 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. DNA Starter Kit 2-Group Set $62 (DNASK-02) • 1-Group Set $34 (DNASK-01) Triphosphate Expansion Pack $12 (DNASK-PEP) ! WARNING: CHOKING HAZARD CAUTION: Science Education Product Nucleotide Please see bottom of page 2 for details. Triphosphates Adenosine Triphosphate Mini Model

Take your exploration of energy metabolism to the next level with our improved, 3D-printed plaster model of adenosine triphosphate (ATP) - the universal currency of energy. The model is based on the atomic coordinates of this important nucleotide. Both the second and third phosphates are joined to the model with magnets - allowing students to easily move from AMP (adenosine monophosphate) to ADP (adenosine diphosphate) and ATP. This simple ! WARNING: CHOKING HAZARD model will change the way your students think about glycolysis and the citric acid cycle. ! WARNING: SMALL MAGNETS 4” Plaster Model $88 (ATPMM) © Adenosine Mini Model

CAUTION: Science Education Product Also see DNA Discovery Kit (page 11). Triphosphate Please see bottom of page 2 for details.

3dmoleculardesigns.com 11 ...where molecules become real TM

2018 Molecules of Life Collection©

The Molecules of Life Collection features plaster models of the 4 major types DOUBLE-STRANDED DNA 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. Your DNA exists as a double helix. Two complementary strands of DNA wrap around each other to form a right-handed double helix. This double helix contains complementary A-T and G-C base pairs. In 2001, researchers determined the of biomolecules — nucleic acids, proteins, lipids and carbohydrates. Since the exact nucleotide sequence of the 3.2 billion base pairs of the human genome.

PROTEINS COMPLEX CARBOHYDRATES Plants use glucose units to build two dierent linear Your body produces polymers — either starch or cellulose. You, as a human approximately 50,000 being, have an enzyme (protein) that cuts o the individual dierent proteins, each biomolecules exist and interact in an aqueous environment, water is also included. glucose units of starch — but not cellulose — so that glucose with a specic shape can be oxidized to release its energy. When you eat a meal, that allows it to some of the glucose is stored in a branched polymer called perform a specic glycogen. Glycogen rapidly releases glucose to function. Aquaporins provide energy between meals. are channel proteins that facilitate the Two single building block models go with each biomolecule. A major teaching point selective diusion of water in single le across a cell membrane. Thirteen variants of aquaporin Glycogen have been identied in humans. Each is is that large complex biomolecules are made of small, simple building block units. composed of 250-300 NUCLEOTIDE 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 the water molecules nucleotides together to make long polymers. Cells use the unique sequence of nucleotides in DNA as a code All models are built to the same scale — 20 million times their real size. rapidly through to build the correct sequence of amino acids in a protein. the membrane.

HO To see water molecules passing CARBOHYDRATE Cellulose through the channel, nd the Carbohydrates — also called sugars — green monomer and gently separate its section from the are energy-rich molecules that provide rest of the model. fuel for your body. Glucose is a carbohydrate that plants build from AMINO ACIDS carbon dioxide and energy from the sun in a process called Starch photosynthesis. The energy stored in carbohydrates is released Amino acids are the monomer building blocks of The yellow dot highlights the sixth carbon in each glucose. proteins. There are 20 amino acids — each with a when 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. join together in a distinct sequence — specied by your DNA — they spontaneously fold into a Molecules of LifeMolecules Collection LIPID compact shape following basic principles of ICE STRUCTURES Phospholipids are unusual The models sit on a 24” x 22” placemat that includes a description of each structure. chemistry and physics. molecules with two distinct Water can exist in any one of three states — a gas, liquid properties. One portion of the or solid (ice). At 0o C (32o Fahrenheit) the thermal motion molecule is a long water-avoiding of the water molecules slows to the point that stable WATER (hydrophobic) carbon tail. The hydrogen bonds form between the molecules and an ice Life happens in water. The human body is about other portion is a water-seeking lattice forms. Ice oats since ice lattices are less dense than 70% water. This unique polar solvent provides CELL MEMBRANES (hydrophilic) phosphate group. liquid water. This causes lakes to freeze from the top down, the medium in which the macromolecules of Phospholipid bilayers form Individual 8.5” x 11” student workstation mats are available online to download and In your cells, phospholipid insulating the life beneath. Water molecules can form more your cells oat. Biomolecules interact with cell membranes to separate molecules spontaneously than a dozen crystalline structures depending on temperature each other in your cells following basic the inside of your cells from the assemble into a lipid bilayer and pressure; however, nearly all ice on the Earth's surface and in principles of chemistry and physics. outside. The hydrophobic nature with the hydrophobic carbon its atmosphere is a hexagonal phase denoted as ice I . of a phospholipid bilayer prevents h tails buried and hidden from the the free movement of most small polar water molecules. The molecules into and out of your cells. polar phosphate portion of print. Proteins embedded in cell membranes the phospholipids are 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 UILDING BLOCKS

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 The entire set includes 17 models: DNA, adenosine monophosphate, aquaporin, 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 Indicates one monomer within the polymer monosaccharides, respectively. Since they interact in an aqueous environment, we have Each of the structures featured is essential to sustain life. included water as one of the Molecules of Life. Lipids are a diverse group of molecules Large biological polymers — DNA, proteins, starch, glycogen and cellulose, and Phosphorous Carbon that interact with each other through “hydrostatic interactions” rather than covalent membranes — are composed of smaller “building block” monomers — nucleotides, bonds, and generally are not large enough to be considered macromolecules. amino acids, glucose and phospholipids. Oxygen Nitrogen Aquaporin and other proteins embed in the cell membrane to allow water and ...where molecules become real TM other molecules or ions to pass in and out of the cell. Hold the aquaporin and cell Remember that these structures are dynamic and exible, not rigid like the plaster Sulfur Hydrogen* models included in the Molecules of Life Collection©. membrane models next to each other, as you discuss water transport through the 3dmoleculardesigns.com asparagine, cell membrane, phospholipid, starch, glycogen, cellulose, glucose, ice cbm.msoe.edu cell membrane. *Not all hydrogens are shown on these images. When teaching the concepts related to the Molecules of Life featured above, All monomers and polymers featured on the placemat and in the models are shown you may want to use 3D Molecular Designs’ Water Kit©, DNA Discovery Kit©, at the same scale. They are magnied 20 million times. Flow of Genetic Information Kit©, Amino Acid Starter Kit©, and Phospholipid & The size of an atom is the same in all molecules in which it is present. For example, Membrane Transport Kit©. oxygen, shown in red, is the same size whether it is in a nucleotide, amino acid, Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2015 Version 4.5 structure and water molecule. sugar, phospholipid or water.

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-P) 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 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©

This is the must-have kit 3DMD customers have been asking for! Our new Flow of Genetic Information Kit© will first allow your students to:

• Model DNA replication using color-coded, foam nucleotides and a placemat. • Model RNA 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.

Lessons and activities are available online.

1-Group Set $114 (FGIK-01) Flow of GeneticKit Information 3-Group Set $308 (FGIK-03) 6-Group Set $552 (FGIK-06) Additional DNA & RNA Nucleotide Set $23 (FGIK-ANS) Side Chain Expansion Pack $27 (FGIK-SCEP) tRNA Expansion Pack $19 (FGIK-TEP) ! WARNING: CHOKING HAZARD Also see DNA Discovery Kit© and DNA Starter Kit© (page 11), DNA Mini Model (page 10), CAUTION: Science Education Product Molecules of Life© (page 12) and Tour of a Human Cell© (page 14). Please see bottom of page 2 for details.

Demo DNA Nucleotides© © The sky is the limit to what you can teach using these large-scale, color-coded foam nucleotides. Begin by teaching 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 DNA Discovery Kit© and DNA Starter Kit© (page 11), DNA Mini Model (page 10), Molecules of Life© (page 12) and Tour of a Human Cell© (page 14). Demo DNA Nucleotides ! WARNING: CHOKING HAZARD 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 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 TM lled with water, ions, sugars, ATP, ...where molecules become real 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 2018 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 David Goodsell Cellular Landscapes 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 David Goodsell, PhD, scientist, author and artist of all things small, creates cellular landscapes that accurately illustrate the size, 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 shape and distribution of proteins in their natural environment of the cell. These unique images connect the molecular world, structure of molecules, and bioinformatics. inferred by X-ray crystallography and NMR spectroscopy, with the cellular world, observed by light and electron microscopy.

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 signalThese recognition particle laminated (B) and added to theprints new proteins by oligosaccharyl of Goodsell’s transferase (H). Finally, the new stunning proteinswater like giantin (A) colorand GM130 (B) guide paintings the vesicles to the right place. illustratethe proteins are properly biology modied and sorted, theyin are delivereda dimension throughout the clathrin coat not falls o and seenthe vesicle is guided in to its otherultimate 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), Grp94instructional (D), calnexin and protein disulde tools.endoplasmic reticulum Adjacent and destroyed by the proteasome text (J). identifies the structures and explains their functions. Whether teaching the flow of genetic 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 information, the many jobs of proteins, energy metabolism or the immunology of a flu shot, these landscapes may be the missing piece in your current collection of instructional tools. Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016 Version 1.1 - 2/2016

This illustration simulates what K we would see if we could © magnify a portion of a living cell by 1,500,000 times. At this H The Tour of a Human Cell Panorama will take your students from the nucleus to G magnication, atoms would be B about the size of a grain of salt, H cells would be the size of huge the outer cell membrane. In the nucleus, DNA is wrapped around histones forming buildings, and you would be roughly one-fourth the size of the nucleosomes. RNA polymerase unwraps the DNA and makes mRNA which is earth in height, allowing you to J H walk across the continent in a few steps. All of the macromolecules delivered through nuclear pore complexes to ribosomes where antibody proteins in the cell are shown, including A B proteins, nucleic acids, carbohy- A I drates and lipid bilayers, but all of are made and delivered into the endoplasmic reticulum. Vesicles carry the protein the smaller molecules have been A D omitted for clarity. In reality, the empty spaces in this picture are through the Golgi and kinesin motor proteins pull the antibodies to the cell lled with water, ions, sugars, ATP, and many other small molecules. A membrane — a wonderful example of the immunology of your flu shot. 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. Tour of a Human Cell Grand Panorama 23” x 11’ $88 (DGTHC-GP) C J C ©

C © B Tour of a Human Cell Panorama 11” x 70” $51 (DGTHC-P) 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. I Tour of a Human Cell J Goodsell. It reveals a previously unseen level of F This illustration simulates what A we would see if we could K biological scale. Light and electron microscopy may be magnify a portion of a living cell by 1,500,000 times. At this H G magnication, atoms would be B used to explore the ultrastructure of cells, and X-ray B about the size of a grain of salt, H cells would be the size of huge buildings, and you would be crystallography and NMR spectroscopy may be used to roughly one-fourth the size of the earth in height, allowing you to J H walk across the continent in a few reveal the atomic structure of individual puried steps. All of the macromolecules in the cell are shown, including A molecules, but there is currently no way to observe proteins, nucleic acids, carbohy- B A I drates and lipid bilayers, but all of the smaller molecules have been A D directly the structure of living cells at the molecular level. To purchase this book, visit springer.com omitted for clarity. In reality, the empty spaces in this picture are lled with water, ions, sugars, ATP, Instead, this illustration is synthesized by combining or your favorite bookseller. E 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 experimental data on cellular ultrastructure, the atomic 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 structure of molecules, and bioinformatics. J C C B C D G E G B The Machinery of Life E F F 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 are then processed: capping enzymes (D) protect one end and polyadenylate of the nucleus through nuclear pore complexes (H). These pores span the they are being made. The transporterThis image is taken from nds The Machinery new of Life by David proteins S. by looking for a special isomerase (E) and cyclophilin (F) assist in the folding of the new proteins. Polysaccharide 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 Nucleus. The nucleus is the cell’s library, storing the delicate strands of Endoplasmic Reticulum. With so many compartments, our cells need ways Golgi Apparatus. The transport vesicles carry the new proteins to the J Cytoplasm and Cell Membrane. Goodsell. It reveals a previously unseen level of F A 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.biological This scale. Light signal and electron microscopy sequence may be 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 DNA and protecting them from the rigors of the cytoplasm. Much of the DNA is of sorting and transporting new proteins to their proper destinations. For many used to explore the ultrastructure of cells, and X-ray Golgi,B a set of membrane-bounded sacs stacked like plates. Huge tethering through the cytoplasm to the cell membrane, pulled by kinesin (A) along microtubules crystallography and NMR spectroscopy may be used to which is then protected by the polyadenylate binding protein (F). Our DNA importin proteins (I), which carry other molecules in and out. The nuclear ribosome, and it is quickly recognizedreveal the atomic structure by of individual a signal puried recognition particle (B) and added to the new proteins by oligosaccharyl transferase (H). Finally, the new 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 proteins, such as the antibodies made by this plasma cell, the journey starts with the molecules, but there is currently no way to observe 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. directly the structure of living cells at the molecular level. To purchase this book, visit springer.com 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. 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 endoplasmicInstead, reticulum this illustration is synthesized surface. by combining Later, or your favoritethe bookseller. signal sequence is clippedE 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 The cytoplasm of our cells is lled with enzymes and other proteins performing their and protect the DNA. When the DNA is needed, it is unwrapped, unwound, and experimental data on cellular ultrastructure, the atomic 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 synthesizedstructure of molecules, and bioinformatics. 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 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. TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as 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 tetheredenzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with ...where molecules become real 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 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. cbm.msoe.edu TM with transport proteins (A) that bind to ribosomes and guide new proteins inside as enzymes of glycolysis, and other synthetic enzymes. The cytoplasm is criss-crossed with 3dmoleculardesigns.com ...where molecules become real cbm.msoe.edu 3dmoleculardesigns.com

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 Neuromuscular Synapse Poster E The Machinery of Life 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 The NeuromuscularDNA and protecting them from the rigors of the cytoplasm. Much of the DNA is polymerase (E) addsSynapse a repeated string of adenine nucleotides to the other end, double-layered Poster nuclear membrane and control the tra c of a diverse collection of (right)of sorting and transporting new proteinsillustrates to their proper destinations. For many signal sequence of amino acids. Thisthe signal sequence is the rst thing molecularmade by the chains are made by a series of enzymes in the membrane (G) and nallyinteractionsGolgi, a set of membrane-bounded sacs stacked like plates. Huge tethering foundthe base of the Y-shaped antibody are trimmed at 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. Neuromuscular Neuromuscular 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 Synapse Poster 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, 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

cbm.msoe.edu 3dmoleculardesigns.com

a neuromuscular synapse — where vesicles filled with the neurotransmitter, acetylcholine, Copyright 3D Molecular Designs - All Rights Reserved - 2009, 2016 Version 1.1 - 2/2016 are fusing with the membrane of the pre-synaptic neuron. Following vesicle fusion, the acetylcholine diffuses across the synaptic space to bind to acetylcholine receptors found in the membrane of the muscle cell. Acetylcholinesterase is entangled in the synaptic space, where it breaks down the neurotransmitter, ending neuronal signaling. Neuromuscular Synapse Poster © 23” x 30” $29 (DGNSP) Also see Tour of a Human Cell© (above), the DNA Discovery Kit© and DNA Starter Kit© (page 11) and the following mini models: Nucleosome, Ribosomes and tRNA (page 16), Antibody, Hemagglutinin and Influenza Virus Capsule (page 17).

Neuromuscular Synapse Poster©

14 ...where molecules become real TM

NEW Flu Fight: Immunity & Infection Panorama©

What molecular mechanisms protect our bodies from influenza virus infection? What events transpire when those defenses © 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 population each year. These cellular, watercolor landscapes will take your students from infection of the ciliated epithelial cells that line the upper respiratory tract, through virus neutralization by antibodies in the mucosal barrier. Influenza – in the absence of antibodies – breaches the barrier and binds in the cell membrane before fusing with the endosomal membrane and finally releasing segmented viral RNA genome into the cytoplasm. Illustrate your discussions about infectious disease and immunity with this beautiful, accurate panorama that identifies key proteins and other molecular structures and explains their functions! Flu Fight: Immunity & Infection Panorama© 23” x 66” $56 (DGFFP) Infection Panorama Flu Fight: Immunity and Fight: Flu

See our Antibody and Antigen Models on page 17! Enhance your students’ conceptual understanding of immunity and infection with multiple models. Use the Antibody and Antigen Models to actively simulate the antibody binding and specificity illustrated in the Flu Fight Panorama. Also see Tour of a Human Cell© on the previous page. Mitochondria and E. coli Posters

In the Mitochondria Poster© (left) your students will see the large protein complexes of the electron transport chain which create the electrochemical gradient that powers ATP synthase to build ATP. ATP is then transported out of the mitochondrion by the adenine nucleotide translocator and diffuses through

the channels in the VDAC protein in the outer membrane. Posters

The E. coli Poster© (right) illustrates the inside of an E. coli

cell — magnified 1 million times. The molecular complexity of coli E. this bacterial cell is emphasized in this image which features a large flagellum and the motor proteins that power its rotation and a variety of transmembrane proteins that function in transporting molecules into and out of the cell. Also shown are the ribosomes and associated proteins that support bacterial protein synthesis and the DNA, along with the DNA and RNA polymerases that function in replication and transcription. 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 DNA Discovery Kit© and DNA Starter 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

2018 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)

Large and Small Ribosome Mini Models

Ribosome Mini Models Mini Ribosome Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath won the Nobel Prize in Chemistry in 2009 for studies of the structure and function of the ribosome. (nobelprize.org) Large and Small Large and Small Protein synthesis becomes understandable as your students see the 3 tRNAs of the small (30S) 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 peptide bond 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) Also see Flow of Genetic Information Kit© (page 13) and Tour of a Human Cell© (page 14).

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 to a growing chain during protein synthesis. Transfer RNAs fold into 3-D structures, stabilized by hydrogen bonding between complementary bases. In this model, the phosphate backbone of the tRNA is white, the 4 bases are red, the anticodon is blue and the 3’- end (where the amino acid is bound) is yellow. 3.5” Plaster Model $76 (TRNAMM)

Nylon tRNA

Nylon tRNA RNA folds into complex 3-D shapes — just like proteins. This nylon model of tRNA shows the details of this complex 3-D structure — complete with the A-T and G-C base-pairs that stabilize the structure. The model allows students to explore the anti-codon of the tRNA, and the 3’ end of tRNA where the charged amino acid is added. 3” Nylon Model $175 (NTRNAM) Also see DNA Discovery Kit© and DNA Starter Kit© (page 11), Flow of Genetic Information Kit© (page 13) and Tour of a Human Cell© (page 14).

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 – NEW Durable Plastic!

Incorporate the concepts of protein structure and function while teaching the immune system using our antibody model – now printed in more durable plastic. Antibodies are composed of 12 repeating immunoglobulin folds. Our model highlights the four polypeptides – two yellow heavy chains and two red light chains – that join to form the iconic “Y” shaped molecule. Students will model how an antibody binds to two antigens (purple globular structures) found on an influenza virus protein. 1 8.5” Plastic Antibody and 2 3.5” Antigen Models $52 (ANTPM)

Don’t forget about our Flu Fight: Immunity & Infection Panorama on page 15! Enhance your students’ Models Antigen conceptual understanding of immunity and infection with multiple models. Use the Antibody and Antigen Models to actively simulate the antibody binding and specificity illustrated in the panorama. Plastic models will break if abused.

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. Models magnet-dock onto the base and can be removed for closer examination. 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 antibodies in Mini Model response to the flu vaccine. Hemagglutinin 6.5” Tall Plaster Mini Model $114 (HAMM)

Influenza Virus Capsules

Influenza is an RNA virus with a roughly spherical lipid envelope, which is colored yellow on our schematic model. The outside of the virus capsule is covered with 3 specific proteins: hemagglutinin (HA, purple), neuraminidase (NA, pink) and the M2 channel (blue). These 3 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 — some colored red and some colored yellow — to represent a re-assorted virus emerging from a host cell simultaneously infected with a swine flu virus and an avian flu virus (H1N1 swine flu). 6’’ Plaster Model $625 (IVCM6)

4” Plaster Mini Model $450 (IVCM4) VirusInfluenzaCapsules 6” Plaster Model is not eligible for discounts

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

2018 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 reductase – the enzyme that was shown to be defective in Noah and Alexis Beery. The map Human Sepiapterin Human Sepiapterin 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. Sepiapterin Reductase Mini Model $137 (SPRMM)

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. 3” Dopamine Biosynthesis Model $37 (DBMM) 3” Serotonin Biosynthesis Model $39 (SBMM) © © Dopamine Biosynthesis Model Serotonin Biosynthesis Model Also see DNA Discovery Kit and DNA Starter Kit (page 11), Flow of Genetic Information Kit© (page 13) and Tour of a Human Cell© (page 14).

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

Engage your classroom with hands-on modeling of neuronal communication! Students can use the colorful foam pieces in our new 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. • And much, much more! Synapse Construction Kit Construction Synapse Assembly instructions, lessons and activities are available online. 1-Group Set $99 (SCK-01) • 3-Group Set $288 (SCK-03) • 6-Group Set $561 (SCK-06) Also see Phospholipid & Membrane Transport Kit© (page 5) and Neuron Modeling Kit© (below).

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 activites are available online. Modeling Kit Neuron

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. Amino Acid Building Block Models $30 (AABB) Block Models Also see Amino Acid Starter Kit© (page 7). Amino Acid Building Acid Amino

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

2018 Alpha Helix & Beta Sheet Models

The alpha helix and the beta sheet represent the 2 important protein structural elements of secondary protein structure. We feature 4 models for your students to Beta Sheet Models Beta explore — 2 alpha helix and 2 beta sheet models. Alpha Helix & Alpha Helix & β Both alpha sheet plaster models are derived from helix E of the -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) Alpha Helix with Side Chains Beta Sheet with Side Chains Also see β-Globin Mini Models (page 6), Green Fluorescent Protein Mini Model (below) and Alpha Helix & Beta Sheet Construction Kit (below). Alpha Helix & Beta Sheet Alpha Sheet Helix & Beta © Construction Kit Alpha Helix & Beta Sheet Construction Kit

This 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. ©

Zinc Finger Mini Model Mini Model Mini Zinc Finger A zinc finger is a short (~30 amino acid) protein motif that is often found in proteins that bind to DNA. Zif268 is a DNA binding protein that contains 3 consecutive zinc fingers. 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) Also see Amino Acid Starter Kit© (page 7).

Protein Model Mini Green Fluorescent Protein Mini Model Green Fluorescent

This 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. 3” Plaster Model $112 (GFPMM) Also see Amino Acid Starter Kit© (page 7).

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.

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 $107 (MTAB-12) • 6-Tube Set $58 (MTAB-06) • 2-Tube Set $22 (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 $9.25 (MTBR-01) Also see Amino Acid Starter Kit© (page 7). Modeling Mini Toobers Water Tattoos

With these fun Water Tattoos you can simultaneously reward your students and reinforce concepts related to the three states of water. Each set contains 50 Water Vapor Tattoos, 50 Liquid Water Tattoos and 50 Frozen Water Tattoos. Water States of Water Tattoos Set $31 (SWTS) Tattoos

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

Fall 2017 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

Sign up to receive our monthly email newsletter and stay up-to-date about 3D Molecular Designs’ latest products and events! We Appreciate Your Feedback!

Please let others know how our products worked for your students. Visit our website, choose the kit, model or poster you’d like to review and scroll to the bottom of the page to add your feedback. Have you developed a great activity for one of our kits or models? Consider sharing your lessons, assessments and 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 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.

22 ...where molecules become real TM

The Genetic Codon Chart© and Genetic Codon Circle© can be used in conjunction with 3DMD’s popular Amino Acid Starter © Kit©, β-Globin Folding Kit© and Insulin mRNA to Protein Kit© — which introduce your students to a standard color scheme: hydrophobic amino acids are yellow, polar amino acids are white, acidic amino acids are red, basic amino acids are blue and cysteines are green. By applying this same color scheme to the codon posters, your students can easily build a seamless connection between the triplet codon in mRNA and the chemical property of the amino acid it encodes. Genetic Codon Chart© (24” x 30”) $24 each (GCCA) Genetic Codon Circle© (30” x 24”) $24 each (GCCB)

The Genetic Codon Chart© Best when used with the Amino Acid Starter Kit© and Amino Acid Starter Kit Poster© (Page 7), β-Globin Folding Kit© and Map of the Human β-Globin Gene (page 6), Insulin mRNA to Protein © © © Kit (page 9) and Flow of Genetic Information Kit (page 13). The Genetic Codon Circle Posters 3DMD Genetic Codon

Science Olympiad Protein Modeling Kits

The Science Olympiad Protein Modeling Event continues this year as a trial event focusing on two proteins found on the surface of the influenza virus. Visit 3dmoleculardesigns.com/Science-Olympiad-Protein-Modeling-Kits.htm to purchase Pre-Build Kits and Practice Kits. Sign up at cbm.msoe.edu/scienceOlympiad/ to receive Regional and State On-Site Kits, Exams and Judging Materials free of charge. Pre-Build Kit $31 (SOPB18) • Practice Kit $23 (SOPK18) • Practice Judging Model $40 (SOPJM) Pre-Build Kit and Amino Acid Starter Kit© Bundle $78.20 (SOAA)

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 Dynamic DNA Kit

If only your students had this innovative new DNA kit… If only we had the funding to buy the press and make the molds! Help us make this Dynamic DNA Kit a reality! Join our crowdfunding campaign in October 2017. Watch our website, newsletter and social media to make sure you’re first to hear when the campaign kicks off - and how Students you can secure Discover a first run kit • Accurate DNA and RNA with your • Nucleotide base pairing donation. • Semi-conservative replication • Continuous & discontinuous strands • RNA transcription • 5’ to 3’ synthesis • Major and minor grooves • Phosphodiester bonds • DNA packaging • Adenosine triphosphate

dynamicdnakit.com