Note: Intro -- Title Page -- Copright Page -- Preface -- Table of Contents -- Section I Ribosome structure -- 1 Ribosome crystallography: From early evolution to contemporary medical insights -- 1. Introduction -- 2. Hibernating bears stimulated ribosome crystallization -- 3. The ribosome is a polymerase -- 4. Structural disorder with functional meaning -- 5. On the ribosomal tunnel and initial nascent protein folding -- 6. Antibiotics targeting the ribosome: strategies, expectations and problems -- 7. The ribosomal core is the optimized vestige of an ancient entity -- 8. Conclusion -- 9. Future prospects -- Acknowledgements -- References -- 2 Structural studies on decoding, termination and translocation in the bacterial ribosome -- 1. Introduction -- 2. Studies on decoding -- 2.1. Insights from studies on the 30S subunit -- 2.2. Structures of the ribosome with elongation factor Tu and aminoacyl tRNA -- 3. Studies on termination -- 4. The peptidyl transferase center in the 70S ribosome -- 5. Structure of a post-translocation complex of the ribosome with elongation factor G -- 6. A structure of a ribosome recycling factor -- 7. Conclusions -- Acknowledgements -- References -- 3 Structural studies of complexes of the 70S ribosome -- 1. Introduction -- 2. Something old, something new: Antibiotics and the ribosome -- 2.1. The macrolides and chloramphenicol revisited -- 2.2. The tuberactinomycins -- 3. Insights into the regulation of bacterial protein synthesis -- 3.1. Regulation at the level of initiation: EF-P and the first peptide bond -- 3.2. Nascent chains as regulators of protein synthesis: The TnaC leader peptide -- Acknowledgements -- References -- 4 Interaction of bacterial ribosomes with mRNA and tRNA as studied by X-ray crystallographic analysis -- 1. Introduction. , 2. How does the ribosome maintain the reading frame of messenger RNA during protein synthesis? -- 2.1. Overview of the mRNA path through the ribosome -- 2.2. Network of interactions of the ribosome with the mRNA downstream of the A-site codon -- 2.3. Role of tRNA modifications in stabilizing mRNA-tRNA interactions on the ribosome. mRNA kink between P- and E-site codons -- 2.4. Interactions of the ribosome with the mRNA region upstream of the P-site codon -- 2.5. mRNA movement on the ribosome -- 3. Stabilization of tRNA in the A site of the 70S ribosome -- References -- 5 Genetic and crystallographic approaches to investigating ribosome structure and function -- 1. Introduction -- 2. Thermus thermophilus as a model system -- 2.1. Genetics of T. thermophilus -- 2.2. Ribosomal genes and antibiotic-resistance mutations -- 2.3. Streptomycin resistance and dependence -- 2.4. Communication between ribosomal protein S12 and EF-Tu -- 3. X-ray crystallography of mutant 30S subunits -- 3.1. Probing the structural basis for streptomycin dependence -- 3.2. Restructuring of the 30S subunit by rRNA modification -- 4. Conclusions -- References -- 6 The packing of ribosomes in crystals and polysomes -- 1. Introduction -- 2. Organization of polysomes -- 2.1. Polysomes in bacteria -- 2.2. Ribosome positioning in polysomes -- 2.3. Evidence for inter-ribosome regulation -- 3. Packing of ribosomes in crystals -- 4. Reconciling ribosome packing in crystals and polysome function -- 4.1. Translation initiation in bacteria -- 4.2. A functional role for protein L9 in polysomes -- 5. Conformational dynamics of ribosomes within polysomes -- 6. Conclusions -- Acknowledgements -- References -- 7 Crystal structure of the eukaryotic 80S ribosome -- 1. Introduction -- 2. Overall view of the 80S yeast ribosome -- 3. Ribosomal domain movements in the ratcheted state. , 4. Rearrangement of ribosome functional sites upon ratcheting -- 5. Concluding remarks -- References -- 8 Structure and function of organellar ribosomes as revealed by cryo-EM -- 1. Introduction -- 2. The structure of the mammalian mitochondrial ribosome -- 2.1. The small subunit of mammalian mitochondrial ribosomes -- 2.2. The large subunit of mammalian mitochondrial ribosomes -- 2.3. Mammalian mitochondrial translation initiation factors -- 2.4. Elongation factor G of mammalian mitochondria -- 3. Structure of a protistan mitochondrial ribosome -- 3.1. Small subunit of the Leishmania mitoribosome -- 3.2. Large subunit of the Leishmania mitoribosome -- 4. Structure of a chloroplast ribosome -- 4.1. Small subunit of the chloroplast ribosome -- 4.2. Large subunit of the chloroplast ribosome -- 5. The polypeptide exit tunnels of the organellar ribosomes -- 6. Conclusions -- Acknowledgements -- References -- 9 Modifications of ribosomal RNA: From enzymes to function -- 1. Introduction -- 2. Modifications of rRNA stabilize ribosome structure -- 3. Modifications in rRNA enhance ribosome interaction with ligands -- 4. Modifications of rRNA unify ribosome interaction with ligands -- 5. Modification of rRNA as an "assembly checkpoint" -- 6. Modification of rRNA as a "quality mark" in ribosome assembly -- 7. rRNA modification as antibiotic resistance mechanism -- 8. rRNA modification and regulation of gene expression -- References -- Section II Recruiting the ribosome for translation -- 10 Insights into translation initiation and termination complexes and into the polysome architecture -- 1. Structure and function of bacterial translation initiation complexes -- 1.1. Pre-initiation: mRNA binding and adaptation onto the 30S subunit -- 1.2. Translation initiation factors -- 1.3. The structure of translation initiation complexes. , 2. The three-dimensional architecture of bacterial and eukaryotic polyribosomes -- 3. Structure of bacterial translation termination complexes -- 3.1. Bacterial termination complexes with RF1 and RF2 -- 3.2. Bacterial termination complexes with the class-II release factor RF3 -- References -- 11 Initiation of bacterial protein synthesis with wild type and mutated variants of initiation factor 2 -- 1. Introduction -- 2. Roles of initiation factors in rapid and accurate formation of the 30S PIC -- 3. Roles of initiation factors and initiator tRNA in subunit joining -- 4. Roles of GTP and GTP hydrolysis in initiation of mRNA translation -- 5. Alternative models of subunit joining and 70S IC formation -- 5.1. Roles of GTP hydrolysis and Pi release in subunit joining -- 5.2. IF2 interaction with the L12 protein of the 50S subunit promotes fast subunit joining -- 6. Accuracy of initiator tRNA selection in initiation of mRNA translation -- 7. Initiation with non-formylated Met-tRNAi -- 8. IF2 mutants active in subunit joining in the absence of tRNA or GTP -- 9. Conclusion -- Acknowledgements -- References -- 12 Translation initiation at the root of the cold-shock translational bias -- 1. Background -- 2. Nature and molecular basis of the cold-shock translational bias -- 2.1. Cis-acting elements -- 2.2. Trans-acting elements -- 2.3. Multiple origin of the cold-shock translational bias -- 2.4. Factors responsible for positive translational bias -- 2.5. Factors responsible for negative translational bias -- 3. Origin of the IFs/ribosome stoichiometric imbalance -- References -- 13 Recruiting knotty partners: The roles of translation initiation factors in mRNA recruitment to the eukaryotic ribosome -- 1. Introduction -- 2. Individual initiation factors -- 2.1. eIF3 -- 2.2. eIF4E -- 2.3. eIF4G -- 2.4. eIF4A -- 2.5. Other helicases in translation initiation. , 2.6. eIF4B -- 2.7. eIF4H -- 2.8. PABP -- 3. Conclusion -- References -- 14 The mechanism of ribosome recycling in eukaryotes -- 1. Introduction -- 2. Translation termination in eukaryotes -- 3. Recycling of mammalian post-TCs by initiation factors at low Mg2+ concentrations -- 4. Functions of protein ABCE1 -- 4.1. ABCE1-mediated recycling of mammalian post-TCs -- 4.2. The structure of ABCE1 and its relationship to function -- 4.3. Evidence for the involvement of ABCE1 in translation termination and initiation -- 4.4. Involvement of ABCE1 in cellular processes other than translation -- 5. Alternative mechanisms for recycling of ribosomes in yeast? -- 6. Perspectives -- Acknowledgements -- References -- Section III Decoding, fidelity, and peptidyl transfer -- 15 The specific interaction between aminoacyl-tRNAs and elongation factor Tu -- 1. Introduction -- 2. Structures of the interface between EF-Tu and aa-tRNA -- 3. Conformity and thermodynamic compensation -- 4. How amino acid and tRNA specificity are achieved -- 5. Estimating binding affinities and explaining T-stem sequence variation -- 6. EF-Tu affinity and ribosomal function -- Acknowledgement -- References -- 16 Mechanisms of decoding and peptide bond formation -- 1. Introduction -- 2. The mechanism of decoding -- 2.1. The kinetic scheme of decoding -- 2.2. Initial binding -- 2.3. Codon recognition -- 2.4. GTPase activation -- 2.5. GTP hydrolysis by EF-Tu on the ribosome -- 2.6. Pi release and the conformational change of EF-Tu -- 2.7. aa-tRNA accommodation -- 3. Fidelity of aa-tRNA selection -- 3.1. Error frequency -- 3.2. Molecular mechanism of tRNA selection -- 3.3. Trade-off between speed and accuracy -- 4. Peptide bond formation -- 4.1. Structures of reaction intermediates -- 4.2. Enzymology of the peptidyl transfer reaction -- References. , 17 Sense and nonsense recognition by the ribosome.

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