Protein Synthesis and Ribosome Structure

Transcription

1 Protein Synthesis and Ribosome Structure Translating the Genome Edited by Knud H. Nierhaus and Daniel N. Wilson WILEY- VCH WILEY-VCH Veriag GmbH & Co. KCaA

2 Contents Preface XV 1 A History of Protein Biosynthesis and Ribosome Research 1 Hans-Jorg Rheinberger 1.1 Introduction The Archaeology of Protein Synthesis - The 1940s: Forgotten Paradigms Basic Mechanisms - The 1950s Steps toward an in vitro Protein Synthesis System Amino Acid Activation and the Emergence of Soluble RNA From Microsomes to Ribosomes Models The Golden Age of Translation - The 1960s From Enzymatic Adaptation to Gene Regulation: Messenger RNA A Bacterial in vitro System of Protein Synthesis and the Cracking of the Genetic Code The Functional Dissection of Translation The Structural Dissection of the Ribosome s: A Brief Synopsis 35 References 38 2 Structure of the Ribosome 53 Cregor Blaha 2.1 General Features of the Ribosome and Ribosomal Subunits A Special Feature of the 50S Subunit: The Tunnel Features of the Ribosomal Subunits at Atomic Resolution The Domain Structure of the Ribosomal Subunits Interactions of RNA with RNA or Struts and Bolts in the Threedimensional Fold of rrna: Coaxial Stacking and A-minor Motifs Coaxial Stacking A-minor Motifs Ribose Zippers and Patches of A-minor Motifs Canonical Ribose Zipper Single-base Ribose Zipper 71

3 VI Contents 2.6 Progress and New Developments in Understanding rrna Structures K-turn Lonepair Triloop Classification of Lonepair Triloops Systemizing Base Pairs Systemizing RNA Structural Elements RNA-protein Interactions Problem of RNA Recognition Chemistry of RNA-protein Interactions rrna-protein Interaction 81 References 82 3 Ribosome Assembly Assembly Of The Prokaryotic Ribosome 85 Knud H. Nierhaus Introduction Processing of rrnas Precursor Particles and Reconstitution Intermediates Assembly-initiator Proteins Proteins Essential for the Early Assembly: The Assembly Gradient Late-assembly Components Proteins Solely Involved in Assembly Assembly Maps 99 References Eukaryotic Ribosome Synthesis 107 Denis L.J. Lafontaine Introduction Prelude Why so many RRPs? (Pre-)ribosome Assembly, the Proteomic Era ^Ribosomal RNA Processing, Getting there Ribosomal RNA Modification: A Solved Issue? Ribose Methylation, Pseudouridines formation and the snornas The Emergence of the snornas Non-ribosomal RNA Substrates for the snornas Possible function(s) of RNA modifications Base methylation U3 snornp, the 'SSU Processome', and the Central Pseudoknot SnoRNA Synthesis and Intranuclear Trafficking SnoRNAs Synthesis 125

4 Contents VII Non-core snornp Proteins required for snorna Accumulation Interactions between Cleavage Factors and Core snornp Proteins SnoRNAs Trafficking CB/NB are Conserved Sites of Small RNP Synthesis Ribosome Intranuclear Movements and Ribosome Export The Cytoplasmic Phase of Ribosome Maturation Regulatory Mechanisms, all along And Now... What's Next? Epilogue Useful WWW links 135 References trna and Synthetases trna: Structure and Function 145 Viter Marquez and Knud H. Nierhaus Introduction Secondary Structure Tertiary Structure trna Modifications Recognition of trna by trna synthetase: Identity Elements Is the trna Cloverleaf Structure a Pre-requisite for the L-shape? Other Functions of trna outside the Ribosomal Elongation Cycle Human Neurodegenerative Disorders Associated with Mitochondrial trnas 162 References Aminoacylations of trnas: Record-keepers for the Genetic Code 169 Liu's Ribas de Pouplana and Paul Schimmel Introduction The Operational RNA Code Extant Aminoacyl-tRNA Synthetases The Origin of Aminoacyl-tRNA Synthetase Classes: Two Proteins bound to one* trna A Common Genetic Origin for all Aminoacyl-tRNA Synthetases? Evolution of Extant Enzymes prior to LUCA Changes in Acceptor Stem Identity Elements Correlate with Changes in the Code 180 References mrna Decay and RNA-degrading Machines in Prokaryotes and Eukaryotes 185 Agamemnon J. Carpousis and Marc Dreyfus 5.1 Summary 185

5 VIM Contents 5.2 Introduction mrna Decay in E. coli mrna Decay in S. cerevisiae A Comparison of mrna Decay in E. coli and S. cerevisiae RNase E Specificity: A Role in Translation Arrest? The E. coli RNA degradosome The Autoregulation of RNase E and PNPase Synthesis: A Link between Bulk Translation and mrna Stability RNA-degrading Machines in other Organisms DEAD-box ATPases Perspective 202 References trna Locations on the Ribosome 207 Knud H. Nierhaus 6.1 trnas Move through Functional Sites on the Ribosome Visualization of trnas on the Ribosome trna-ribosome Contacts 215 References Initiation of Protein Synthesis Initiation of Protein Synthesis in Eubacteria 219 Daniel N. Wilson Overview of I nitiation in Eubacteria Specialized initiation events: translational coupling, 70S initiation and leaderless mrnas Initiation Factor 1 Binds to the Ribosomal A-site The Domain Structure of Bacterial IF Interaction Partners of IF The Role of the IF2-dependent GTPase Activity The Mystery of the IF3-binding Site on the 30S Subunit 233 "' References Mechanism and Regulation of Protein Synthesis Initiation in Eukaryotes 241 Alan G. Hinnebusch, Thomas E. Dever, and Nahum Sonenberg Introduction Overview of Translation-initiation Pathways in Eukaryotes and Prokaryotes Conservation and diversity of translation-initiation factors among bacteria, archaea and eukaryotes Genetic assays for in vivo functions of eif Generation of Free 40S Subunits and 40S Binding of Met-tRNA 251

6 Dissociation of Idle 80S Ribosomes Components of the eif2/gtp/met-trna Ternary Complex The GEF eif2b regulates ternary complex formation Binding of Ternary Complex and mrna to the 40S Ribosome is Stimulated by eif elfia Stimulates Ternary Complex Binding to 40S Subunits and Participates in AUG Selection During Scanning Binding of Ribosomes to mrna The Ends of Eukaryotic mrnas Contain Distinctive Conserved Structures Ribosome Binding to mrna is Stimulated by the eif4 Factors Circularization of mrna via eif4g-pabp Interaction Translational Control by mrna Circularization Regulation of eif4 Function by Phosphorylation eif4e Phosphorylation eif4e-4e-bps eif4g Phosphorylation eif4b Phosphorylation Translational Control by Paips - PABP Interacting Proteins AUG Recognition during Scanning AUG is the Predominant Signal for Initiation and is Selected by Proximity to the 59-end by the Scanning Mechanism The Anticodon of trna, eif2 Subunits, elfl, and eif5 are Determinants of AUG Selection during Scanning elfl plays a role in TC binding, scanning, and AUG selection A eif5 Functions as a GTPase Activating Protein for eif2 in AUG Selection and Subunit Joining Joining of 60S Subunits to 40S Ribosomal Complexes eif5b Catalyzes a Second GTP-dependent Step in Translation Initiation GTPase Switch Regulates Ribosome Affinity of eif5b and Governs Translational Efficiency IRES-mediated Translation Initiation Future Prospects 310 References The Elongation Cycle 323 Knud H. Nierhaus 8.1 Models of the Elongation Cycle The Hybrid-site Model for Elongation The Allosteric Three-site Model (a-e Model; Reciprocal Coupling between the A- and E-sites) 329 Contents IX

7 X Contents 8.2 Decoding and A-site Occupation Some General Remarks about Proofreading Discrimination against Noncognate aa-trnas Decoding of an aa-trna (Cognate versus Near-cognate aa-trnas) Roles of EF-Tu Mimicry at the Ribosomal A-site Translational Errors The PTF Reaction A Short Intermission: Two Enzymatic Principles of PTF Activity Chemical Concept: A Transient Covalent Bond between Active Center and Substrate(s) Physical Concept: The Template Model Data from the Crystal Structures Why both the Physical and Chemical Concepts for Peptide-bond Formation? The Translocation Reaction Conservation in the Elongation Factor-G Binding Site Dynamics within the Ribosome 359 References Termination and Ribosome Recycling 367 Daniel N. Wilson 9.1 Introduction Stop Codon Recognition and Release of the Nascent Polypeptide Chain The Bacterial Class I Decoding Release Factors The Structure of RF2 and Translational Mimicry The Two-domain Functional Model for RF Identifying Functional Important Regions within the Decoding RFs Codon Recognition Domain of Bacterial RFs: the.termination Signal Codon Recognition Domain of Bacterial RFs: the "Tripeptide Motif" Peptidyl-tRNA hydrolase function of bacterial RFs: domain III and the GGQ motif Large Conformational Changes Associated with RF2 Binding to the Ribosome The Trigger for RF-mediated Release of the Nascent Chain and the Outcome Eukaryotic Class I Termination Factors Stop-codon Recognition is Associated with Domain I of erfl 386

8 Contents XI erfl-mediated Polypeptide Release Dissociation of the Post-termination Complex Eubacterial RF3 Dissociates the Class I Termination Factors Eukaryotic RF3: Dissociation versus Delivery of erfl Ribosome Recycling RRF Mediates Ribosome Recycling in Eubacteria 391 References The Mechanism of Recoding in Pro- and Eukaryotes 397 Elizabeth 5. Poole, Louise L. Major, Andrew G. Cridge, and Warren P. late 10.1 Introduction Maintaining Decoding Accuracy and the Reading Frame The Use of a Stop Signal for both Elongation and Termination of Protein Synthesis The Mechanism for Sec Incorporation at UGA Sites in Bacterial mrnas The Gene Products The Mechanism of Sec Incorporation The Competition between Sec Incorporation and Canonical Decoding of UGA by RF Mechanism for Sec Incorporation at UGA Sites in Eukaryotic and Archaeal mrnas The Gene Products The Mechanism of Sec Incorporation at Specific UGA Stop Codons Why does Recoding Occur at Stop Signals? The Stop Signal of Prokaryotic Genomes - Engineered for High Efficiency Decoding? The Stop Signal of Eukaryotic Genomes - Diversity Contributes to Recoding Readthrough of a Stop Signal: Decoding Stop as Sense Bypassing o,f a Stop Codon: 'Free-wheeling' on the mrna Frameshifting Around Stop or Sense Codons Forward Frameshifting: the +1 Event Programed -1 Frameshifting: A Common Mechanism used by Many Viruses During Gene Expression Conclusion 424 References Regulation of Ribosome Biosynthesis in Escherichia coli 429 Madina Iskakova, Sean R. Connell, and Knud H. Nierhaus Overview of Ribosome Biosynthesis Regulation 429

9 XII Contents 11.1 Regulation of rrna Synthesis Organization of rrna Operons and Elements of rrna Promoters Models for rrna Regulation Stringent Response Regulation of r-protein Synthesis Some General Remarks Various Models for r-protein Regulation spc operon S10 operon a operon str operon IF3 operon Conclusion 445 References 446 "12 Antibiotics and the Inhibition of Ribosome Function 449 Daniel N. Wilson 12.1 Introduction The Inhibition of Protein Synthesis in Bacteria Inhibitors of Initiation Kasugamycin Edeine Pactamycin Evernimicin and Avilamycin Antibiotic Inhibitors of Ribosome Assembly Inhibitors of the Elongation Cycle Antibiotic Action and A-site Occupation Tetracycline: An Inhibitor of A-site Occupation Antibiotics Affecting the Fidelity of Translation Inhibitors of EF-Tu-mediated Reactions Inhibitors of Peptide-bond Formation and Nascent 'Chain Progression Puromycin and Blasticidin S mimic the CCA end of trnas Sparsomycin Prevents A-site Binding and Stimulates P-site Binding Antibiotic Overlap in the PTF Center: chloramphenicol, Anisomycin and the Lincosamides Blocking the Progression of the Nascent Chain by the Macrolide Antibiotics Streptogramins New Classes of Translation Inhibitors; the Oxazolidinones and Novel Ribosome Inhibitors 496

10 Contents XIII Translocation Inhibitors Thiostrepton and Micrococcin Viomycin Blocks Coupled GTPase Activity Spectinomycin Interferes with EF-G Binding Fusidic Acid is the Counterpart of Kirromycin Inhibitors of Termination, Recycling and trans-translation Termination Recycling Trans- translation Mechanisms Causing Drug Resistance Modification of the Antibiotic Blockage of Transport (without Modification of the Drug) Overproduction of the Inhibited Substrate (Target Dilution) Bypassing or Replacement of the Inhibited Reaction Alteration of the Target Site Active Protection of the Target by a Third Component Future Perspectives 512 References The Work of Chaperones 529 Jean-Herve Alix 13.1 From The Levinthal Paradox To The Anfinsen Cage The Folding Machines The Trigger Factor (TF) The DnaK/DnaJ/GrpE System The GroEL/GroES System Other Chaperones HSP Clp/HSPlOO Family DegP Periplasmic Chaperones Pili Chaperones Small HSPs Endoplasmic Reticulum (ER) Chaperones Intramolecular Chaperones Chaperone Networks De novo Protein Folding Protein Disaggregation Posttranslational Quality Control Chaperones and Stress A.I The Heat-shock Response and its Regulation 547

11 XIV Contents Thermotolerance Who Detects Stress? Assembly and Disassembly of Macromolecular Complexes Protein Translocation Across Membranes New Horizons in Chaperone Research HSP90 and the Pandora's Box of Hidden Mutations Chaperones and Prions Chaperones and Ribosome Biogenesis RNA Chaperones Chemical Chaperones Medical implications Chaperoning the chaperones 553 References 554 Index 563