DOCSLIB.ORG

The Role of the Signal Recognition Particle in Protein Targeting and Mrna Protection

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of the Signal Recognition Particle in Protein Targeting and Mrna Protection International Journal of Molecular Sciences Review SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection Morgana K. Kellogg, Sarah C. Miller, Elena B. Tikhonova and Andrey L. Karamyshev * Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; [email protected] (M.K.K.); [email protected] (S.C.M.); [email protected] (E.B.T.) * Correspondence: [email protected]; Tel.: +1-806-743-4102 Abstract: Signal recognition particle (SRP) is an RNA and protein complex that exists in all domains of life. It consists of one protein and one noncoding RNA in some bacteria. It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals. In the eukaryotic cyto- plasm, SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm. It was demonstrated recently that SRP also possesses an earlier unknown function, the protection of mRNAs of secretory proteins from degradation. In this review, we analyze the progress in studies of SRPs from different organisms, SRP biogenesis, its structure, and function in protein targeting and mRNA protection. Keywords: ribosome; mRNA translation; signal recognition particle (SRP); protein targeting and transport; protein sorting; signal sequence; protein quality control; translational control Citation: Kellogg, M.K.; Miller, S.C.; Tikhonova, E.B.; Karamyshev, A.L. SRPassing Co-translational Targeting: 1. Introduction The Role of the Signal Recognition Cells have a very complex network of a number of cellular organelles surrounded Particle in Protein Targeting and by different membranes. To maintain their viability, cells constantly transport proteins mRNA Protection. Int. J. Mol. Sci. from the place of their synthesis to these organelles or outside of the cells. Cell proteomics 2021, 22, 6284. https://doi.org/ predicts that there are more than 109 proteins in a single human cell [1]. Therefore, directing 10.3390/ijms22126284 proteins to their correct destination is an important process for all cells. The correct identifi- cation and targeting of proteins are vital to ensure that the proteins are accurately folded, Academic Editor: Lasse Lindahl active, and delivered to the right place at the right time with the precise amount of protein needed. The cost of mistargeting, however, is large; many diseases are attributed to the Received: 30 April 2021 aberrant localization of proteins, which results in cytotoxic aggregation, degradation, loss Accepted: 5 June 2021 of expression, and misfolding of proteins. The cells have evolved several mechanisms and Published: 11 June 2021 many specific protein targeting signals to ensure fast, efficient, and accurate targeting of proteins to prevent these problems. In this review, we briefly discuss different protein tar- Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in geting signals and then focus on one of the major secretory pathways, the signal recognition published maps and institutional affil- particle (SRP) pathway, SRP biogenesis, SRP structure, and SRP cellular function. iations. 2. Protein Targeting Signals Proteins contain information about subcellular localization in the form of special sequences for their transport. Cells rely on the recognition of these specific signals (lo- calization sequences) embedded in the structure of polypeptide chains to sort proteins Copyright: © 2021 by the authors. to their appropriate cellular compartments. This recognition, targeting, and transport Licensee MDPI, Basel, Switzerland. This article is an open access article can occur during or after protein synthesis at the ribosome, and these pathways are distributed under the terms and referred to as co-translational and post-translational processes, respectively, shown in conditions of the Creative Commons Figure1A. Targeting to mitochondria, the nucleus, and peroxisomes occurs mostly post- Attribution (CC BY) license (https:// translationally, while protein targeting and importing into the endoplasmic reticulum creativecommons.org/licenses/by/ (ER) occurs co-translationally, directed by its cytosolic targeting factor, SRP, the signal 4.0/). recognition particle [2–7]. Int. J. Mol. Sci. 2021, 22, 6284. https://doi.org/10.3390/ijms22126284 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 22 Int. J. Mol. Sci. 2021, 22, 6284 while protein targeting and importing into the endoplasmic reticulum (ER) occurs co-transla-2 of 21 tionally, directed by its cytosolic targeting factor, SRP, the signal recognition particle [2–7]. FigureFigure 1. 1. CellularCellular organelles organelles and and protein protein target targetinging signals signals in inthe the mammalian mammalian cell. cell. (A) Protein (A) Protein tar- getingtargeting signals signals.. Within Within the cell, the cell,there there are many are many different different signals signals that direct that directproteins proteins for proper for proper local- ization.localization. Nuclear Nuclear (salmon (salmon circle) and circle) nucleolar and nucleolar (yellow (yellowcircle) signals circle) include signals the include NLS and the NES. NLS Sig- and nalsNES. to Signals the endoplasmic to the endoplasmic reticulum reticulum include the include signal the peptide signal and peptide KDEL, and which KDEL, prevents which secretion prevents fromsecretion the ER. from The the cytoplasmic ER. The cytoplasmic signals (light signals tan) (light are generally tan) are generally not well-defined not well-defined and include andinclude every- thingeverything that does that not does contain not contain a signal a signalpeptide. peptide. Peroxisome Peroxisome (purple (purple circle) circle)signals signals are PTS1 are and PTS1 PTS2. and The Golgi (magenta stacked ovals) signals include N-linked glycosylations, resident proteins are PTS2. The Golgi (magenta stacked ovals) signals include N-linked glycosylations, resident proteins retained via HEAT repeats, and errant proteins are recaptured with COPI and COPII vesicles. Tar- are retained via HEAT repeats, and errant proteins are recaptured with COPI and COPII vesicles. geting signals to the lysosome (gray circle) include phosphorylated mannose, or DXXLL or YXXφ. ' Post-translationalTargeting signals totargeting the lysosome to the (gray plasma circle) membrane include phosphorylated(black outline) uses mannose, the absence or DXXLL of mannose- or YXX . 6-p,Post-translational while co-translational targeting signals to the include plasma membranethe signal peptide. (black outline) Mitochondria uses the (blue) absence have of their mannose- own mitochondrial6-p, while co-translational targeting signal signals peptide. include Extracellu the signallar matrix-bound peptide. Mitochondria proteins (white (blue) background) have their own are targetedmitochondrial using a targeting signal peptide. signal peptide. All co-translation Extracellularal mechanisms matrix-bound of targeting proteins (white are designated background) by two are starstargeted flanking using the a signal signal peptide. (e.g., *signal All co-translational peptide*). (B) Diagram mechanisms of a ofprotein targeting with are a signal designated sequence by two. A signalstars flanking sequence the features signal a (e.g., positi *signalve N-region peptide*). (yellow), (B) Diagram a hydrophobic of a protein (H) middle with a signalregion sequence. (blue), a C- A regionsignal sequence(green), and features a region a positive that will N-region become (yellow),the mature a hydrophobic protein once (H)signal middle peptidase region (cleavage (blue), a site demarcated by black triangles) cleaves off the signal sequence (red). C-region (green), and a region that will become the mature protein once signal peptidase (cleavage site demarcated by black triangles) cleaves off the signal sequence (red). Post-translational targeting includes signals to the peroxisome, nuclear entrance and exit signals,Post-translational Golgi membrane targeting localization, includes signalssignals toto thethe peroxisome,lysosome, and nuclear mitochondrial entrance andsig- nalexit peptides. signals, Golgi Many membrane post-translational localization, targetin signalsg features to the lysosome, have been and characterized. mitochondrial Peroxi- signal somespeptides. have Many two signals: post-translational peroxisome targeting targeting features signal have1 (PTS1) been and characterized. 2 (PTS2). The Peroxisomes most com- monhave PTS1 two signals:signal is peroxisome a serine-lysine-leucine targeting signal at the 1 carboxy-end (PTS1) and 2 [8] (PTS2). and is The recognized most common by the PTS1 signal is a serine-lysine-leucine at the carboxy-end [8] and is recognized by the recep- tor encoded by PEX5 on the peroxisomal membrane [9]. PTS2 uses the PEX5L and PEX7 receptors in mammals for transport into the peroxisome [10]. Nuclear targeting signals Int. J. Mol. Sci. 2021, 22, 6284 3 of 21 have both entry and exit codes: a nuclear localization signal (NLS) to target the nucleus and a nuclear exit signal (NES) to leave. Nuclear localization signals have a general consensus sequence featuring positively charged amino acids with linker regions in between, called a bipartite signal [11]. Importins, either by themselves or with cofactors, recognize NLSs to permit proteins to enter the nucleus. Nuclear exit signals consist of four
Load more

Recommended publications
  • RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA
    GENES AND PROTEINS THAT CONTROL THE SECRETORY PATHWAY Nobel Lecture, 7 December 2013 by RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA. Introduction George Palade shared the 1974 Nobel Prize with Albert Claude and Christian de Duve for their pioneering work in the characterization of organelles interrelated by the process of secretion in mammalian cells and tissues. These three scholars established the modern field of cell biology and the tools of cell fractionation and thin section transmission electron microscopy. It was Palade’s genius in particular that revealed the organization of the secretory pathway. He discovered the ribosome and showed that it was poised on the surface of the endoplasmic reticulum (ER) where it engaged in the vectorial translocation of newly synthesized secretory polypeptides (1). And in a most elegant and technically challenging investigation, his group employed radioactive amino acids in a pulse-chase regimen to show by autoradiograpic exposure of thin sections on a photographic emulsion that secretory proteins progress in sequence from the ER through the Golgi apparatus into secretory granules, which then discharge their cargo by membrane fusion at the cell surface (1). He documented the role of vesicles as carriers of cargo between compartments and he formulated the hypothesis that membranes template their own production rather than form by a process of de novo biogenesis (1). As a university student I was ignorant of the important developments in cell biology; however, I learned of Palade’s work during my first year of graduate school in the Stanford biochemistry department.
    [Show full text]
  • Bacterial Cell Membrane
    BACTERIAL CELL MEMBRANE Dr. Rakesh Sharda Department of Veterinary Microbiology NDVSU College of Veterinary Sc. & A.H., MHOW CYTOPLASMIC MEMBRANE ➢The cytoplasmic membrane, also called a cell membrane or plasma membrane, is about 7 nanometers (nm; 1/1,000,000,000 m) thick. ➢It lies internal to the cell wall and encloses the cytoplasm of the bacterium. ➢It is the most dynamic structure of a prokaryotic cell. Structure of cell membrane ➢The structure of bacterial plasma membrane is that of unit membrane, i.e., a fluid phospholipid bilayer, composed of phospholipids (40%) and peripheral and integral proteins (60%) molecules. ➢The phospholipids of bacterial cell membranes do not contain sterols as in eukaryotes, but instead consist of saturated or monounsaturated fatty acids (rarely, polyunsaturated fatty acids). ➢Many bacteria contain sterol-like molecules called hopanoids. ➢The hopanoids most likely stabilize the bacterial cytoplasmic membrane. ➢The phospholipids are amphoteric molecules with a polar hydrophilic glycerol "head" attached via an ester bond to two non-polar hydrophobic fatty acid tails. ➢The phospholipid bilayer is arranged such that the polar ends of the molecules form the outermost and innermost surface of the membrane while the non-polar ends form the center of the membrane Fluid mosaic model ➢The plasma membrane contains proteins, sugars, and other lipids in addition to the phospholipids. ➢The model that describes the arrangement of these substances in lipid bilayer is called the fluid mosaic model ➢Dispersed within the bilayer are various structural and enzymatic proteins, which carry out most membrane functions. ➢Some membrane proteins are located and function on one side or another of the membrane (peripheral proteins).
    [Show full text]
  • Evidence for an Alternate Pathway for Lysosomal Enzyme Targeting (Oligosaccharides/Lysosomes/Phosphorylation) CHRISTOPHER A
    Proc. NatL Acad. Sci. USA Vol. 80, pp. 775-779, February 1983 Cell Biology Identification and characterization of cells deficient in the mannose 6-phosphate receptor: Evidence for an alternate pathway for lysosomal enzyme targeting (oligosaccharides/lysosomes/phosphorylation) CHRISTOPHER A. GABEL, DANIEL E. GOLDBERG, AND STUART KORNFELD Departments of Internal Medicine and Biological Chemistry, Division of Hematology-Oncology, Washington University School of Medicine, St. Louis, Missouri 63110 Contributed by Stuart Kornfeld, November 3, 1982 ABSTRACT Newly synthesized lysosomal enzymes acquire dence that this cell line is deficient in Man-6-P receptor activity. phosphomannosyl units, which allow bindingofthe enzymes to the We also identify several additional cell lines that lack receptor mannose 6-phosphate receptor and subsequent translocation to activity yet possess high levels ofintracellular hydrolase activity. lysosomes. In some cell types, this sequence ofevents is necessary These data indicate that some cells possess pathways indepen- for the delivery ofthese enzymes to lysosomes. Using a slime mold dent of the Man-6-P receptor for the intracellular transport of lysosomal hydrolase as a probe, we have identified three murine acid hydrolases to lysosomes. cell lines that lack the receptor and one line that contains very low (3%) receptor activity. Each ofthese lines synthesizes the mannose MATERIALS AND METHODS 6-phosphate recognition marker on its lysosomal enzymes, but, Cells. BW5147 mouse lymphoma, P388D1 mouse macro- unlike cell lines with high levels of receptor, the cells accumulate MOPC 315 oligosaccharides containing phosphomonoesters. The receptor- phage, J774.2 mouse macrophage, mouse L cells, deficient lines possess high levels of intracellular acid hydrolase mouse myeloma, Chinese hamster ovary (CHO), and (human) activity, which is contained in dense granules characteristic of ly- HeLa cells were grown in suspension culture in a minimal es- sosomes.
    [Show full text]
  • Control of Protein Function
    3 Control of Protein Function In the cell, precise regulation of protein function is essential to avoid chaos. This chapter describes the most important molecular mechanisms by which protein function is regulated in cells. These range from control of a protein’s location and lifetime within the cell to the binding of regulatory molecules and covalent modifications such as phosphorylation that rapidly switch protein activity on or off. Also covered here are the nucleotide-driven switches in conformation that underlie the action of motor proteins and that regulate many signal transduction pathways. 3-0 Overview: Mechanisms of Regulation 3-1 Protein Interaction Domains 3-2 Regulation by Location 3-3 Control by pH and Redox Environment 3-4 Effector Ligands: Competitive Binding and Cooperativity 3-5 Effector Ligands: Conformational Change and Allostery 3-6 Protein Switches Based on Nucleotide Hydrolysis 3-7 GTPase Switches: Small Signaling G Proteins 3-8 GTPase Switches: Signal Relay by Heterotrimeric GTPases 3-9 GTPase Switches: Protein Synthesis 3-10 Motor Protein Switches 3-11 Regulation by Degradation 3-12 Control of Protein Function by Phosphorylation 3-13 Regulation of Signaling Protein Kinases: Activation Mechanism 3-14 Regulation of Signaling Protein Kinases: Cdk Activation 3-15 Two-Component Signaling Systems in Bacteria 3-16 Control by Proteolysis: Activation of Precursors 3-17 Protein Splicing: Autoproteolysis by Inteins 3-18 Glycosylation 3-19 Protein Targeting by Lipid Modifications 3-20 Methylation, N-acetylation, Sumoylation and Nitrosylation 3-0 Overview: Mechanisms of Regulation Protein function in living cells is precisely regulated A typical bacterial cell contains a total of about 250,000 protein molecules (comprising different amounts of each of several thousand different gene products), which are packed into a volume so small that it has been estimated that, on average, they are separated from one another by a distance that would contain only a few molecules of water.
    [Show full text]
  • The Endomembrane System and Proteins
    Chapter 4 | Cell Structure 121 Endosymbiosis We have mentioned that both mitochondria and chloroplasts contain DNA and ribosomes. Have you wondered why? Strong evidence points to endosymbiosis as the explanation. Symbiosis is a relationship in which organisms from two separate species depend on each other for their survival. Endosymbiosis (endo- = “within”) is a mutually beneficial relationship in which one organism lives inside the other. Endosymbiotic relationships abound in nature. We have already mentioned that microbes that produce vitamin K live inside the human gut. This relationship is beneficial for us because we are unable to synthesize vitamin K. It is also beneficial for the microbes because they are protected from other organisms and from drying out, and they receive abundant food from the environment of the large intestine. Scientists have long noticed that bacteria, mitochondria, and chloroplasts are similar in size. We also know that bacteria have DNA and ribosomes, just like mitochondria and chloroplasts. Scientists believe that host cells and bacteria formed an endosymbiotic relationship when the host cells ingested both aerobic and autotrophic bacteria (cyanobacteria) but did not destroy them. Through many millions of years of evolution, these ingested bacteria became more specialized in their functions, with the aerobic bacteria becoming mitochondria and the autotrophic bacteria becoming chloroplasts. The Central Vacuole Previously, we mentioned vacuoles as essential components of plant cells. If you look at Figure 4.8b, you will see that plant cells each have a large central vacuole that occupies most of the cell's area. The central vacuole plays a key role in regulating the cell’s concentration of water in changing environmental conditions.
    [Show full text]
  • A Mitochondria–Lysosome Transport Pathway
    RESEARCH HIGHLIGHTS Controlling enteric nerve Interestingly, inhibition of integrin signalling The authors used point mutations to establish cell migration or ROCK activity rescued directed migration of that residue Met 44 of actin was essential for the MEFs and normalized the migration of ENCCs F-actin-severing function of Mical. Manipulation A functional gastrointestinal system is in organ cultures. Although the precise function of Mical levels is known to generate abnormal dependent on the enteric nervous system, of Phactr4 remains to be discovered, these data bristle cell processes in Drosophila. In the present which is formed during embryogenesis through demonstrate its role in regulating lamellipodial study, mutation of the Met 44 actin residue colonization of the gut by enteric neural crest actin dynamics through cofilin activity suppressed Mical overexpression phenotypes cells (ENCCs). Now, Niswander and colleagues controlled by integrin and PP1 signalling. CKR and phenocopied Mical loss-of-function effects identify the protein phosphatase 1 (PP1)- and in Drosophila. Together, these findings establish actin-binding protein Phactr4 as a regulator actin as a direct substrate of Mical and reveal of directional and collective ENCC migration a specific oxidation-dependent mechanism (Genes Dev. 26, 69–81; 2012). Actin gets the oxidation to regulate actin filament dynamics and cell Analysis of mouse embryos expressing treatment from Mical processes in vivo. AIZ a Phactr4 mutation known to abolish PP1 binding revealed reduced enteric neuronal Mical, an enzyme mediating redox reactions, numbers and defective organization at is known to promote actin remodelling embryonic day 18.5, and reduced ENCC in response to semaphorin signalling by A mitochondria–lysosome numbers in the gut at earlier stages (E12.5).
    [Show full text]
  • 4 Membrane Trafficking
    Trafficking 1 MCB 110 - Spring 2008- Nogales 4 MEMBRANE TRAFFICKING I Introduction: secretory pathway A. Protein Synthesis and sorting B. Methods to study cytomembranes II Endoplasmic Reticulum A. Smooth ER B. Rough ER C. Synthesis of proteins in membrane-bound ribosomes • The signal hypothesis • Synthesis of membrane proteins D. Glycosylation in the ER III Golgi IV Vesicle Transport A. COPII-coated Vesicles B. COPI-coated Vesoicles C. Clathrin-coated Vesicles V Lisosomes A. Phagocytosis B. Autophagy VI Endocytosis Suggested Reading: Lodish, Chapter 5, 5.3; Chapter 16, 16.1 to 16.3; Chapter 17 Alberts, Chapters 12 and 13 Trafficking 2 MCB 110 - Spring 2008- Nogales I Introduction to the Secretory Pathway The eukaryotic cell is filled with membranous organelles that form part of an integrated and dynamic system shuttling material across the cell Trafficking 3 MCB 110 - Spring 2008- Nogales The biosynthetic or secretory pathway includes the synthesis of proteins in the ER, their modification in the ER and Golgi, and their transport to different destinations such as the plasma membrane, lysosomes, vacuoles, etc. In constitutive secretion materials are transported in a continual manner. In regulated secretion , materials are stored in secretory granules in the periphery of the cell and discarded in response to a particular stimulus (e.g. nerve cells, cells producing hormones or digestive enzymes). Materials are transported in vesicles that move along microtubules, powered by motor proteins. Sorting is facilitated by receptors localized in particular membranes. Trafficking 4 MCB 110 - Spring 2008- Nogales Methods to Study Cytomembranes Visualization by electron microscopy Dynamic localization by autoradiography and pulse-chase Trafficking 5 MCB 110 - Spring 2008- Nogales Trafficking 6 MCB 110 - Spring 2008- Nogales Use of GFP constructs Movement of proteins through the secretory pathway has been followed using a Green Flourescence Protein (GFP).
    [Show full text]
  • The Signal Recognition Particle
    P1: GDL May 22, 2001 22:53 Annual Reviews AR131-22 Annu. Rev. Biochem. 2001. 70:755–75 Copyright c 2001 by Annual Reviews. All rights reserved THE SIGNAL RECOGNITION PARTICLE Robert J. Keenan1, Douglas M. Freymann2, Robert M. Stroud3, and Peter Walter3,4 1Maxygen, 515 Galveston Drive, Redwood City, California 94063; e-mail: [email protected] 2Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611; e-mail: [email protected] 3Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143; e-mail: [email protected] 4The Howard Hughes Medical Institute, University of California, San Francisco, California 94143; e-mail: [email protected] Key Words Alu domain, SRP, SRP54, Ffh, SRP receptor, FtsY, signal sequence, GTPase, SRP9/14, SRP RNA ■ Abstract The signal recognition particle (SRP) and its membrane-associated re- ceptor (SR) catalyze targeting of nascent secretory and membrane proteins to the protein translocation apparatus of the cell. Components of the SRP pathway and salient fea- tures of the molecular mechanism of SRP-dependent protein targeting are conserved in all three kingdoms of life. Recent advances in the structure determination of a number of key components in the eukaryotic and prokaryotic SRP pathway provide new insight into the molecular basis of SRP function, and they set the stage for future work toward an integrated picture that takes into account the dynamic and contextual properties of this remarkable cellular machine. CONTENTS INTRODUCTION ................................................ 756 by UNIVERSITY OF CHICAGO LIBRARIES on 11/05/07. For personal use only. COTRANSLATIONAL PROTEIN TARGETING ..........................756 Annu.
    [Show full text]
  • 1519038862M28translationand
    Paper No. : 15 Molecular Cell Biology Module : 28 Translation and Post-translation Modifications in Eukaryotes Development Team Principal Investigator : Prof. Neeta Sehgal Department of Zoology, University of Delhi Co-Principal Investigator : Prof. D.K. Singh Department of Zoology, University of Delhi Paper Coordinator : Prof. Kuldeep K. Sharma Department of Zoology, University of Jammu Content Writer : Dr. Renu Solanki, Deen Dayal Upadhyaya College Dr. Sudhida Gautam, Hansraj College, University of Delhi Mr. Kiran K. Salam, Hindu College, University of Delhi Content Reviewer : Prof. Rup Lal Department of Zoology, University of Delhi 1 Molecular Genetics ZOOLOGY Translation and Post-translation Modifications in Eukaryotes Description of Module Subject Name ZOOLOGY Paper Name Molecular Cell Biology; Zool 015 Module Name/Title Cell regulatory mechanisms Module Id M28: Translation and Post-translation Modifications in Eukaryotes Keywords Genome, Proteome diversity, post-translational modifications, glycosylation, phosphorylation, methylation Contents 1. Learning Objectives 2. Introduction 3. Purpose of post translational modifications 4. Post translational modifications 4.1. Phosphorylation, the addition of a phosphate group 4.2. Methylation, the addition of a methyl group 4.3. Glycosylation, the addition of sugar groups 4.4. Disulfide bonds, the formation of covalent bonds between 2 cysteine amino acids 4.5. Proteolysis/ Proteolytic Cleavage 4.6. Subunit binding to form a multisubunit protein 4.7. S-nitrosylation 4.8. Lipidation 4.9. Acetylation 4.10. Ubiquitylation 4.11. SUMOlytion 4.12. Vitamin C-Dependent Modifications 4.13. Vitamin K-Dependent Modifications 4.14. Selenoproteins 4.15. Myristoylation 5. Chaperones: Role in PTM and mechanism 6. Role of PTMs in diseases 7. Detecting and Quantifying Post-Translational Modifications 8.
    [Show full text]
  • A Clearer Picture of the ER Translocon Complex Max Gemmer and Friedrich Förster*
    © 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2020) 133, jcs231340. doi:10.1242/jcs.231340 REVIEW A clearer picture of the ER translocon complex Max Gemmer and Friedrich Förster* ABSTRACT et al., 1986). SP-equivalent N-terminal transmembrane helices that The endoplasmic reticulum (ER) translocon complex is the main gate are not cleaved off can also target proteins to the ER through the into the secretory pathway, facilitating the translocation of nascent same mechanism. In this SRP-dependent co-translational ER- peptides into the ER lumen or their integration into the lipid membrane. targeting mode, ribosomes associate with the ER membrane via ER Protein biogenesis in the ER involves additional processes, many of translocon complexes. These membrane protein complexes them occurring co-translationally while the nascent protein resides at translocate nascent soluble proteins into the ER, integrate nascent the translocon complex, including recruitment of ER-targeted membrane proteins into the ER membrane, mediate protein folding ribosome–nascent-chain complexes, glycosylation, signal peptide and membrane protein topogenesis, and modify them chemically. In cleavage, membrane protein topogenesis and folding. To perform addition to co-translational protein import and translocation, distinct such varied functions on a broad range of substrates, the ER ER translocon complexes enable post-translational translocation and translocon complex has different accessory components that membrane integration. This post-translational pathway is widespread associate with it either stably or transiently. Here, we review recent in yeast (Panzner et al., 1995), whereas higher eukaryotes primarily structural and functional insights into this dynamically constituted use it for relatively short peptides (Schlenstedt and Zimmermann, central hub in the ER and its components.
    [Show full text]
  • Protein Targeting Or Protein Sorting
    Protein targeting or Protein sorting Refer Page 1068 to 1074 Principles of Biochemistry by Lehninger & Page 663 Baltimore Mol Cell Biology • Protein targeting or Protein sorting is the process of delivery of newly synthesized proteins to their proper cellular destinations • Proteins are sorted to the endoplasmic reticulum (ER), mitochondria, chloroplasts, lysosomes, peroxisomes, and the nucleus by different mechanisms • The process can occur either during protein synthesis or soon after synthesis of proteins by translation at the ribosome. • Most of the integral membrane proteins, secretory proteins and lysosomal proteins are sorted to ER lumen from where these proteins are modified for further sorting • For membrane proteins, targeting leads to insertion of the protein into the lipid bilayer • For secretory/water-soluble proteins, targeting leads to translocation of the entire protein across the membrane into the aqueous interior of the organelle. • Protein destined for cytosol simply remain where they are synthesized • Mitochondrial and chloroplast proteins are first completely synthesized and released from ribosomes. These are then bound by cytosolic chaperone proteins and delivered to receptor on target organelle. • Nuclear proteins such as DNA and RNA polymerases, histones, topoisomerases and proteins that regulate gene expression contain Nuclear localization signal (NLS) which is not removed after the protein is translocated. Unlike ER localization signal sequence which is at N terminal, NLS ca be located almost anywhere along the
    [Show full text]
  • Cell Wall Ribosomes Nucleus Chloroplast Cytoplasm
    Cell Wall Ribosomes Nucleus Nickname: Protector Nickname: Protein Maker Nickname: Brain The cell wall is the outer covering of a Plant cell. It is Ribosomes read the recipe from the The nucleus is the largest organelle in a cell. The a strong and stiff and made of DNA and use this recipe to make nucleus directs all activity in the cell. It also controls cellulose. It supports and protects the plant cell by proteins. The nucleus tells the the growth and reproduction of the cell. holding it upright. It ribosomes which proteins to make. In humans, the nucleus contains 46 chromosomes allows water, oxygen and carbon dioxide to pass in out They are found in both plant and which are the instructions for all the activities in your of plant cell. animal cells. In a cell they can be found cell and body. floating around in the cytoplasm or attached to the endoplasmic reticulum. Chloroplast Cytoplasm Endoplasmic Reticulum Nickname: Oven Nickname: Gel Nickname: Highway Chloroplasts are oval structures that that contain a green Cytoplasm is the gel like fluid inside a The endoplasmic reticulum (ER) is the transportation pigment called chlorophyll. This allows plants to make cell. The organelles are floating around in center for the cell. The ER is like the conveyor belt, you their own food through the process of photosynthesis. this fluid. would see at a supermarket, except instead of moving your groceries it moves proteins from one part of the cell Chloroplasts are necessary for photosynthesis, the food to another. The Endoplasmic Reticulum looks like a making process, to occur.
    [Show full text]