Ribosomes

Ribosomes

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English

Description

Dr. Spirin is a world authority on ribosomes and has published two earlier books in this area in English.
This text is for advanced undergraduates and beginning graduate students and will cover the structure, function, and biosynthesis of ribosomes. Ribosomes are important in protein synthesis, which is currently a hot topic in many different areas of research.

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Published 01 January 1983
Reads 9
EAN13 0306468158
License: All rights reserved
Language English

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Contents
Part I Historical and Fundamental Introduction
Chapter 1 Protein Biosynthesis: Summary and Definitions References
Chapter 2 Messenger RNA and the Genetic Code 2.1. Discovery of mRNA 2.2.Deciphering the Code 2.3.Some Features of the Code Dictionary 2.4.Deviations from the Universal Code 2.5.Structure of mRNA 2.5.1. Primary Structure 2.5.2.Functional Regions 2.5.3.Folding 2.6.Messenger Ribonucleoproteins of Higher Eukaryotes References
Chapter 3 Transfer RNA and AminoacyltRNA Synthetases 3.1.Discovery 3.2.Structure of tRNA 3.2.1. Primary Structure 3.2.2.Secondary Structure 3.2.3. Tertiary Structure 3.3.AminoacyltRNA Synthetases 3.4.Aminoacylation of tRNA 3.5. Specificity of tRNA Aminoacylation 3.5.1. Specificity for Amino Acids 3.5.2.Specificity for tRNA
vii
5
7 8 12 13 14 14 16 18 19 21
23 24 24 26 30 32 36 40 40 40
viii CONTENTS
3.5.3. Specific Modifications of Aminoacyl Residues after Aminoacylation References
Chapter 4 Ribosomes and Translation 4.1. First Observations 4.2.Localization of Ribosomes in the Cell 4.3. Prokaryotic and Eukaryotic Ribosomes 4.4. Sequential Readout of mRNA by Ribosomes; Polyribosomes 4.5.Stages of Translation: Initiation, Elongation, and Termination 4.6. Chemical Reactions and Overall Energy Balance of Protein Biosynthesis 4.7.Cellfree Translation Systems References
Part II Structure of the Ribosome
Chapter 5 Morphology of the Ribosome 5.1. Size, Appearance, and Subdivision into Subunits 5.2.Small Subunit 5.3. Large Subunit 5.4.Association of Subunits into the Complete Ribosome 5.5.Morphology of the Ribosome at 25Å Resolution 5.6.XRay Crystallography of the Ribosome References
Chapter 6 Ribosomal RNA 6.1. Introduction 6.2.Ribosomal RNAs and their Primary StructuresTypes of 6.3.Secondary Structure of Ribosomal RNAs 6.3.1.General Principles 6.3.2.Secondary Structure of the SmallSubunit rRNA 6.3.3. Secondary Structure of the LargeSubunit rRNA 6.3.4.Secondary Structure of 5S rRNA 6.4.Tertiary Structure and Compact Folding of Ribosomal RNAs 6.4.1.General Principles and Properties 6.4.2.Compact Folding of rRNAs 6.4.3.the Folded rRNAsSpecific Shapes of 6.4.4.Conformational Changes of rRNAs 6.4.5.Model of ThreeDimensional Folding of rRNA References
43 44
47 48 50 51 54
55 57 59
63 65 67 68 69 73 73
75 75 77 77 79 83 83 87 87 88 88 90 93 94
Chapter 7 Ribosomal Proteins 7.1. Diversity and Nomenclature 7.2.Primary Structures 7.3.Threedimensional Structures 7.4. Protein Complexes 7.5.Interactions with Ribosomal RNA 7.6.Ribosomal SubunitsDisassembly and Reassembly of 7.6.1.Disassembly 7.6.2.Reassembly (Reconstitution) References
Chapter 8 Mutual Arrangement of Ribosomal RNA and Proteins (Quaternary Structure) 8.1. Peripheral Localization of Proteins on the RNA Core 8.2.Topography of Proteins 8.2.1. Identification of Neighboring Proteins 8.2.2.Measuring Distances between Proteins and Triangulation 8.2.3. ImmunoElectron Microscopy 8.2.4.Exposure of Proteins on the Ribosome Surface 8.3. Topography of RNA 8.3.1.Assignment to Protein Topography 8.3.2.ImmunoElectron Microscopy 8.4. Quaternary Structure References
Part III Function of the Ribosome
Chapter 9 Functional Activities and Functional Sites of the Ribosome 9.1. Working Cycle of the Ribosome 9.2.Methodological Approaches to Localization of Ribosomal Functional Sites 9.3. Binding, Retention, and Sliding of the Message (mRNABinding Site on the Small Subunit) 9.4. Catalysis of Peptide Bond Formation (Peptidyl Transferase on the Large Subunit) 9.5. GTPDependent Binding of Translation Factors (FactorBinding Site on the Large Subunit) 9.6.AminoacyltRNA and Retention of PeptidyltRNABinding of (tRNABinding Sites at the Intersubunit Space) 9.6.1.P Site 9.6.2.A Site
97 99 102 104 105 110 110 112 115
117 119 119 120 121 123 124 124 126 128 128
133
135
136
142
146
151 153 154
ix CONTENTS
x CONTENTS
9.6.3. Entry Site (R or T Site) 9.6.4. Intermediate Positions ("Hybrid Sites") 9.6.5. Exit Site (E Site) 9.7.Ligand Displacements (Translocation) 9.8.The Material and Energy Balance of the Elongation Cycle References
Chapter 10 Elongation Cycle, Step I: AminoacyltRNA Binding 10.1.Codon–Anticodon Interaction 10.1.1.Adaptor Hypothesis and Its Proof 10.1.2.The Concept of Anticodon 10.1.3.Wobble Hypothesis 10.1.4.Corrections to Wobbling Rules 10.1.5.Stereochemistry of Codon–Anticodon Pairing 10.2.Participation of the Elongation Factor 1 (EFTu or eEF1A) in AminoacyltRNA Binding 10.2.1.EFlA and Its Interactions 10.2.2.Binding the Ternary Complex with the Ribosome 10.2.3. Role of GTP and Its Hydrolysis in the Catalysis of AminoacyltRNA Binding 10.3.Inhibitors of AminoacyltRNA Binding 10.3.1.Tetracyclines 10.3.2. Aminoglycosides 10.3.3.Some Indirect Inhibitors 10.4.Miscoding 10.4.1.Misreading of Poly(U) 10.4.2.Stop CodonsLeakiness of 10.4.3. Principal Types of Mispairing 10.4.4. Factors Contributing to Miscoding 10.4.5. Miscoding Level In Vivo under Normal Conditions 10.4.6. Kinetic Mechanisms of Miscoding and Miscoding Correction 10.5.Summary: Sequence of Events and Molecular Mechanisms 10.5.1.Scanning of tRNA Species 10.5.2. Recognition of Anticodon 10.5.3. GTP Hydrolysis 10.5.4. EFTu (EF1A) Release and Correction of Aminoacyl tRNA Selection 10.5.5. Locking of AminoacyltRNA in the A Site 10.5.6. General Scheme References
Chapter 11 Elongation Cycle, Step II: Transpeptidation (Peptide Bond Formation) 11.1.Chemistry of the Reaction 11.2.Energy Balance of the Reaction
155 155 157 157 157 159
163 163 164 164 167 168
169 170 173
175 177 177 178 181 182 182 184 184 184 186
187 188 188 190 190
192 192 192 192
195 198
11.3. Stereochemistry 11.4. Movement of Transpeptidation Products 11.5.Inhibitors 11.5.1.Chloramphenicol 11.5.2.Lincosamides 11.5.3.Macrolides 11.5.4.Streptogramin B 11.5.5.Streptogramin A 11.5.6.4Aminohexose Pyrimidine Nucleoside Antibiotics 11.5.7.Sparsomycin 11.5.8.Anisomycin References
Chapter 12 Elongation Cycle, Step III: Translocation 12.1. Definition and Experimental Tests 12.2. Participation of the Elongation Factor 2 (EFG or eEF2) in Translocation 12.2.1.EF2 Structure 12.2.2.EF2 Interactions 12.2.3. Translocation Intermediate 12.2.4. Role of GTP and Its Hydrolysis in the Catalysis of Translocation 12.3. “Nonenzymatic” (FactorFree) Translocation 12.4. Movement of the Template during Translocation 12.4.1. Triplet Translocation 12.4.2. Nontriplet Translocations (Translocation Errors) 12.4.2.1. Frameshifting at the AminoacyltRNA Binding Step 12.4.2.2.Frameshifting at the Translocation Step 12.4.3. Ribosome Hops 12.5. Mechanics and Energetics of Translocation 12.5.1.Stereochemistry and Mechanics 12.5.2.Energetics 12.6. Inhibitors of Translocation 12.6.1. Aminoglycosides and Aminocyclitols 12.6.2. Viomycin (Tuberactinomycin) 12.6.3. Thiostrepton 12.6.4.Fusidic Acid 12.6.5. Glutarimides 12.6.6. Nonspecific Inhibitory Agents 12.7. Summary: Sequence of Events and Molecular Mechanisms References
Chapter 13 Elongation Rate and Its Modulation 13.1.Elongation Rates in Prokaryotes and Eukaryotes 13.1.1.Transit Time
199 202 204 204 205 206 207 208 208 210 210 211
213
214 214 216 219
219 221 222 222 223
223 225 227 231 231 232 233 233 234 235 235 236 236 236 238
241 241
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xii CONTENTS
13.1.2.Average Elongation Rate and Its Variations 13.1.3.Polyribosome Profile 13.2.Discontinuities in Elongation 13.2.1.Translational Pauses 13.2.2.Modulating Codons 13.2.3. Structural Barriers alone mRNA 13.2.4.Inhibitory Nascent Peptides 13.3.Selective Regulation of Elongation on Different mRNAs 13.4.ElongationTotal Regulation of 13.4.1.Overall Changes in Elongation Rate 13.4.2. Phosphorylation of Elongation Factor 2 13.4.3. Modifications of Elongation Factor 1 13.5.Elongation Toxins 13.5.1.Diphtheria Toxin 13.5.2.Shiga and Shigalike Toxins 13.5.3. 13.5.4. Plant Toxins 13.5.5. Artificial Chimeric Toxins References
Chapter 14 Termination of Translation 14.1.Termination Codons 14.2.Termination Protein Factors 14.3.Ribosomal Site for Binding Termination Factors 14.4.PeptidyltRNAHydrolysis of 14.5.Events during TerminationSequence of References
Chapter 15 Initiation of Translation 15.1.General Principles 15.1.1.Initiation StageSignificance of 15.1.2.Prokaryotic and Eukaryotic Modes of Initiation 15.1.3.Components of Initiation 15.1.4.InitiationSteps of 15.2.Initiation in Prokaryotes 15.2.1.General Characteristics of Prokaryotic Initiation 15.2.2.RibosomeBinding Site and Initiation Codon 15.2.3. Prokaryotic Initiator tRNA 15.2.4.Prokaryotic Initiation Factors 15.2.5.Sequence of Events 15.2.5.1.Step 1 15.2.5.2.Step 2 15.2.5.3. Step 3 15.2.5.4.Step 4 15.2.5.5.Step 5
243 243 244 244 245 247 248 249 250 250 251 252 253 254 255 256 256 257 257
261 263 265 266 266 269
271 271 272 272 274 276 276 277 280 282 283 283 283 283 284 284
15.3. Initiation in Eukaryotes 15.3.1.Characteristics of Eukaryotic mRNA 15.3.2.The Cap Structure and the Initiation Codons 15.3.3. Internal Ribosome Entry Site 15.3.4.Eukaryotic Initiator tRNA 15.3.5. Ribosomal Initiation Factors 15.3.6.mRNAbinding Initiation Factors 15.3.6.1.CapBinding Complex 15.3.6.2. RNA Helicase Complex 15.3.6.3. Ribosomal Complex 15.3.6.4.IRESBinding Proteins 15.3.7. Terminal Enhancers of Initiation 15.3.7.1.Poly(A)Tail 15.3.7.2.Pseudoknot and tRNAlike Domains 15.3.8.Sequence of Events 15.3.8.1.Step l 15.3.8.2. Step 2 15.3.8.3. Step 3 15.3.8.4.Step 4 15.3.8.5. Step 5 References
Chapter 16 Translational Control in Prokaryotes 16.1. General Considerations 16.2. Discrimination of mRNAs 16.3. Translational Coupling 16.3.1.Initiation Induced by Translation of Upstream Cistron 16.3.2. Sequential Translation of Polycistronic Messages via Reinitiation 16.4. Translational Repression 16.4.1.Regulation of Translation of Bacteriophage MS2 RNA 16.4.2. Regulation of Translation of Ribosomal Protein mRNAs 16.4.3.Translational Autoregulation of the Synthesis of ThreonyltRNA Synthetase 16.4.4. Regulation of Translation of Bacteriophage T4 mRNAs 16.5. Antisense Blockade References
Chapter 17 Translational Control in Eukaryotes 17.1. Importance of Translational Control in Eukaryotes 17.2.Total Translational Regulation 17.2.1. Regulation by Modifications of Initiation Factors 17.2.1.1.Phosphorylation of Factor(eIF2) 17.2.1.2. Phosphorylation of Capbinding Factor (eIF4E) 17.2.2.Regulation by mRNP Formation
286 286 287 289 292 293 295 295 296 297 299 300 300 301 303 303 303 303 305 306 306
309 310 312 312
315 319 320 323
330 333 333 335
339 340 340
340 343 344
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CONTENTS
17.3. Discrimination of mRNAs 17.3.1.Discrimination by Initiating Ribosomal Particles 17.3.2.FactorsmRNABinding Initiation Discrimination by 17.3.3. Modulation of Translational Discrimination by Inhibiting Elongation 17.3.4. Modulation of Translational Discrimination by Changing Initiation Rate 17.4. Regulation of Initiation by Upstream Open Reading Frames 17.4.1.ORF SequenceDependent Inhibition of Initiation 17.4.2.ORFMediated Regulation of Yeast Transcription Factor GCN4 17.4.3. ORFInvolving Ribosome Shunting 17.5. Translational Repression 17.5.1.IronResponsive Regulation 17.5.2.Helix UnwindingRepression via Prevention of 17.5.3. Regulation of Ribosomal Protein mRNA Translation 17.5.4. Repression by Prevention of Initiation Complex Movement along mRNA 17.6. mRNA Masking 17.6.1.Masked mRNA in Oocytes and Spermatocytes 17.6.2.mRNA Masking and Unmasking during Embryonic Development 17.6.3. mRNA Masking and Unmasking during Cell Differentiation 17.6.4. Masking and Unmasking of mRNA in Differentiated Cells 17.6.5. Models of mRNA Masking References
Chapter 18 Cotranslational Folding and Transmembrane Transport of Proteins 18.1. Contribution of Ribosomes to Protein Folding 18.1.1.Starting Conformation Set by the Peptidyl Transferase Center 18.1.2.Intraribosomal Tunnel for Nascent Peptide: Does It Exist? 18.1.3.Cotranslational Folding of Nascent Polypeptide 18.2. RibosomeAssociated Molecular Chaperones 18.3. Synthesis of Proteins by Free and MembraneBound Polyribosomes 18.4. Interaction of Translating Ribosomes with Membranes 18.4.1.Early Observations 18.4.2. Initial Nascent Peptide Interactions 18.4.3.Signal Amino Acid Sequence 18.4.3.1.Cleavable Signal Sequence 18.4.3.2. Uncleavable Signal Sequence 18.4.4.the Ribosome/Nascent Chain ComplexInteraction of with the Signal Recognition Particle
345 345 346
347
348 350 350
351 354 355 355 357 359
360 361 361
363 363
364 365 366
371
371 371 373 375
376 378 378 378 379 380 381
382
18.4.5. Interaction of the Ribosome/Nascent Chain/SRP Complex with SRP Receptor on the Membrane 18.5.Cotranslational Transmembrane Translocation of Nascent Polypeptide Chains 18.5.1.Translocation Channel of the Endoplasmic Reticulum Membrane 18.5.2.the Nascent Polypeptide ChainInsertion of into the Endoplasmic Reticulum Membrane 18.5.3. Arrangement of the Nascent Polypeptide Chain in the Endoplasmic Reticulum Membrane 18.6.Cotranslational Covalent Modifications and Folding of the Nascent Polypeptide Chain in the Endoplasmic Reticulum References
Chapter 19 Conclusion: General Principles of Ribosome Structure and Function 19.1.Introduction 19.2.Basic Features of Ribosome Structure 19.2.1.Two Disparate Subparticles (Ribosomal Subunits) 19.2.2.Selffolding of Ribosomal RNA into a Compact Core 19.2.3.Assembly of Various Ribosomal Proteins on RNA Core 19.3.Ribosome FunctionStructural and Biochemical Grounds of 19.3.1.Structural Pockets for Functional Centers 19.3.2. Division of Labor between Ribosomal Subunits 19.3.2.1.the Small SubunitGenetic Functions of 19.3.2.2. Enzymatic Functions of the Large Subunit 19.3.3. LargeBlock Mobility of the Ribosome 19.3.4.GTPDependent Catalysis of Conformational Transitions
Index
384
385
385
387
389
392 393
397 397 397 398 398 399 399 400 401 401 402 404
407
xv CONTENTS