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  • Review Article
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What recent ribosome structures have revealed about the mechanism of translation

Abstract

The high-resolution structures of ribosomal subunits published in 2000 have revolutionized the field of protein translation. They facilitated the determination and interpretation of functional complexes of the ribosome by crystallography and electron microscopy. Knowledge of the precise positions of residues in the ribosome in various states has facilitated increasingly sophisticated biochemical and genetic experiments, as well as the use of new methods such as single-molecule kinetics. In this review, we discuss how the interaction between structural and functional studies over the last decade has led to a deeper understanding of the complex mechanisms underlying translation.

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Figure 1: Structure of the ribosome.
Figure 2: Overview of bacterial translation.
Figure 3: Decoding by the ribosome.
Figure 4: Peptide-bond formation.
Figure 5: EF-G catalysed translocation.
Figure 6: Termination of translation by class I release factors.

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References

  1. Ramakrishnan, V. Ribosome structure and the mechanism of translation. Cell 108, 557–572 (2002)

    Article  CAS  PubMed  Google Scholar 

  2. Ban, N., Nissen, P., Hansen, J., Moore, P. B. & Steitz, T. A. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 289, 905–920 (2000)

    Article  CAS  PubMed  ADS  Google Scholar 

  3. Wimberly, B. T. et al. Structure of the 30S ribosomal subunit. Nature 407, 327–339 (2000)

    Article  CAS  PubMed  ADS  Google Scholar 

  4. Yusupov, M. M. et al. Crystal structure of the ribosome at 5.5 Å resolution. Science 292, 883–896 (2001)

    Article  CAS  PubMed  ADS  Google Scholar 

  5. Gao, H. et al. Study of the structural dynamics of the E. coli 70S ribosome using real-space refinement. Cell 113, 789–801 (2003)

    Article  CAS  PubMed  Google Scholar 

  6. Harms, J. et al. High resolution structure of the large ribosomal subunit from a mesophilic eubacterium. Cell 107, 679–688 (2001)

    Article  CAS  PubMed  Google Scholar 

  7. Schuwirth, B. S. et al. Structures of the bacterial ribosome at 3.5 Å resolution. Science 310, 827–834 (2005)

    Article  CAS  PubMed  ADS  Google Scholar 

  8. Selmer, M. et al. Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313, 1935–1942 (2006)This high-resolution structure of a functional complex of the ribosome has paved the way for many other studies.

    Article  CAS  PubMed  ADS  Google Scholar 

  9. Nikulin, A. et al. Structure of the L1 protuberance in the ribosome. Nature Struct. Biol. 10, 104–108 (2003)

    Article  CAS  PubMed  Google Scholar 

  10. Diaconu, M. et al. Structural basis for the function of the ribosomal L7/12 stalk in factor binding and GTPase activation. Cell 121, 991–1004 (2005)

    Article  CAS  PubMed  Google Scholar 

  11. Karimi, R., Pavlov, M. Y., Buckingham, R. H. & Ehrenberg, M. Novel roles for classical factors at the interface between translation termination and initiation. Mol. Cell 3, 601–609 (1999)

    Article  CAS  PubMed  Google Scholar 

  12. Peske, F., Rodnina, M. V. & Wintermeyer, W. Sequence of steps in ribosome recycling as defined by kinetic analysis. Mol. Cell 18, 403–412 (2005)

    Article  CAS  PubMed  Google Scholar 

  13. Antoun, A., Pavlov, M. Y., Lovmar, M. & Ehrenberg, M. How initiation factors maximize the accuracy of tRNA selection in initiation of bacterial protein synthesis. Mol. Cell 23, 183–193 (2006)

    Article  CAS  PubMed  Google Scholar 

  14. Grigoriadou, C., Marzi, S., Pan, D., Gualerzi, C. O. & Cooperman, B. S. The translational fidelity function of IF3 during transition from the 30 S initiation complex to the 70 S initiation complex. J. Mol. Biol. 373, 551–561 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Milon, P., Konevega, A. L., Gualerzi, C. O. & Rodnina, M. V. Kinetic checkpoint at a late step in translation initiation. Mol. Cell 30, 712–720 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. Tomsic, J. et al. Late events of translation initiation in bacteria: a kinetic analysis. EMBO J. 19, 2127–2136 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Grigoriadou, C., Marzi, S., Kirillov, S., Gualerzi, C. O. & Cooperman, B. S. A quantitative kinetic scheme for 70 S translation initiation complex formation. J. Mol. Biol. 373, 562–572 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carter, A. P. et al. Crystal structure of an initiation factor bound to the 30S ribosomal subunit. Science 291, 498–501 (2001)

    Article  CAS  PubMed  ADS  Google Scholar 

  19. Simonetti, A. et al. Structure of the 30S translation initiation complex. Nature 455, 416–420 (2008)Refs 19 and 20 have shed light on the location of initiation factors in the ribosome.

    Article  CAS  PubMed  ADS  Google Scholar 

  20. Allen, G. S., Zavialov, A., Gursky, R., Ehrenberg, M. & Frank, J. The cryo-EM structure of a translation initiation complex from Escherichia coli. Cell 121, 703–712 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. Valle, M. et al. Locking and unlocking of ribosomal motions. Cell 114, 123–134 (2003)

    Article  CAS  PubMed  Google Scholar 

  22. Myasnikov, A. G. et al. Conformational transition of initiation factor 2 from the GTP- to GDP-bound state visualized on the ribosome. Nature Struct. Mol. Biol. 12, 1145–1149 (2005)

    Article  CAS  Google Scholar 

  23. Allen, G. S. & Frank, J. Structural insights on the translation initiation complex: ghosts of a universal initiation complex. Mol. Microbiol. 63, 941–950 (2007)

    Article  CAS  PubMed  Google Scholar 

  24. Marshall, R. A., Aitken, C. E. & Puglisi, J. D. GTP hydrolysis by IF2 guides progression of the ribosome into elongation. Mol. Cell 35, 37–47 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Antoun, A., Pavlov, M. Y., Andersson, K., Tenson, T. & Ehrenberg, M. The roles of initiation factor 2 and guanosine triphosphate in initiation of protein synthesis. EMBO J. 22, 5593–5601 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rodnina, M. V. & Wintermeyer, W. Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms. Annu. Rev. Biochem. 70, 415–435 (2001)

    Article  CAS  PubMed  Google Scholar 

  27. Blanchard, S. C., Gonzalez, R. L., Kim, H. D., Chu, S. & Puglisi, J. D. tRNA selection and kinetic proofreading in translation. Nature Struct. Mol. Biol. 11, 1008–1014 (2004)

    Article  CAS  Google Scholar 

  28. Xia, T. et al. Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick base pairs. Biochemistry 37, 14719–14735 (1998)

    Article  CAS  PubMed  Google Scholar 

  29. Ogle, J. M. & Ramakrishnan, V. Structural insights into translational fidelity. Annu. Rev. Biochem. 74, 129–177 (2005)

    Article  CAS  PubMed  Google Scholar 

  30. Ogle, J. M. et al. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902 (2001)

    Article  CAS  PubMed  ADS  Google Scholar 

  31. Ogle, J. M., Murphy, F. V., Tarry, M. J. & Ramakrishnan, V. Selection of tRNA by the ribosome requires a transition from an open to a closed form. Cell 111, 721–732 (2002)

    Article  CAS  PubMed  Google Scholar 

  32. Gromadski, K. B. & Rodnina, M. V. Kinetic determinants of high-fidelity tRNA discrimination on the ribosome. Mol. Cell 13, 191–200 (2004)

    Article  CAS  PubMed  Google Scholar 

  33. Stark, H. et al. Ribosome interactions of aminoacyl-tRNA and elongation factor Tu in the codon-recognition complex. Nature Struct. Biol. 9, 849–854 (2002)

    CAS  PubMed  Google Scholar 

  34. Valle, M. et al. Incorporation of aminoacyl-tRNA into the ribosome as seen by cryo-electron microscopy. Nature Struct. Biol. 10, 899–906 (2003)

    Article  CAS  PubMed  Google Scholar 

  35. Villa, E. et al. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. Proc. Natl Acad. Sci. USA 106, 1063–1068 (2009)This paper and ref. 36 report cryoEM structures of an important state of the ribosome at and beyond 7 Å resolution.

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  36. Schuette, J. C. et al. GTPase activation of elongation factor EF-Tu by the ribosome during decoding. EMBO J. 28, 755–765 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Piepenburg, O. et al. Intact aminoacyl-tRNA is required to trigger GTP hydrolysis by elongation factor Tu on the ribosome. Biochemistry 39, 1734–1738 (2000)

    Article  CAS  PubMed  Google Scholar 

  38. Gregory, S. T., Carr, J. F. & Dahlberg, A. E. A signal relay between ribosomal protein S12 and elongation factor EF-Tu during decoding of mRNA. RNA 15, 208–214 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schmeing, T. M. et al. The structure of the ribosome bound to EF-Tu and tRNA. Science 10.1126/science.1179700 (in the press)

  40. Pape, T., Wintermeyer, W. & Rodnina, M. Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome. EMBO J. 18, 3800–3807 (1999)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cochella, L. & Green, R. An active role for tRNA beyond codon:anticodon base pairing. Science 308, 1178–1180 (2005)

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  42. Battle, D. J. & Doudna, J. A. Specificity of RNA-RNA helix recognition. Proc. Natl Acad. Sci. USA 99, 11676–11681 (2002)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  43. Johansson, M., Bouakaz, E., Lovmar, M. & Ehrenberg, M. The kinetics of ribosomal peptidyl transfer revisited. Mol. Cell 30, 589–598 (2008)

    Article  CAS  PubMed  Google Scholar 

  44. Sievers, A., Beringer, M., Rodnina, M. V. & Wolfenden, R. The ribosome as an entropy trap. Proc. Natl Acad. Sci. USA 101, 7897–7901 (2004)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  45. Nissen, P., Hansen, J., Ban, N., Moore, P. B. & Steitz, T. A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000)

    Article  CAS  PubMed  ADS  Google Scholar 

  46. Muth, G. W., Ortoleva-Donnelly, L. & Strobel, S. A. A single adenosine with a neutral pKa in the ribosomal peptidyl transferase center. Science 289, 947–950 (2000)

    Article  CAS  PubMed  ADS  Google Scholar 

  47. Beringer, M., Adio, S., Wintermeyer, W. & Rodnina, M. The G2447A mutation does not affect ionization of a ribosomal group taking part in peptide bond formation. RNA 9, 919–922 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Polacek, N., Gaynor, M., Yassin, A. & Mankin, A. S. Ribosomal peptidyl transferase can withstand mutations at the putative catalytic nucleotide. Nature 411, 498–501 (2001)

    Article  CAS  PubMed  ADS  Google Scholar 

  49. Thompson, J. et al. Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit. Proc. Natl Acad. Sci. USA 98, 9002–9007 (2001)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  50. Katunin, V. I., Muth, G. W., Strobel, S. A., Wintermeyer, W. & Rodnina, M. V. Important contribution to catalysis of peptide bond formation by a single ionizing group within the ribosome. Mol. Cell 10, 339–346 (2002)

    Article  CAS  PubMed  Google Scholar 

  51. Youngman, E. M., Brunelle, J. L., Kochaniak, A. B. & Green, R. The active site of the ribosome is composed of two layers of conserved nucleotides with distinct roles in peptide bond formation and peptide release. Cell 117, 589–599 (2004)

    Article  CAS  PubMed  Google Scholar 

  52. Hansen, J. L., Schmeing, T. M., Moore, P. B. & Steitz, T. A. Structural insights into peptide bond formation. Proc. Natl Acad. Sci. USA 99, 11670–11675 (2002)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  53. Schmeing, T. M., Huang, K. S., Kitchen, D. E., Strobel, S. A. & Steitz, T. A. Structural insights into the roles of water and the 2′ hydroxyl of the P site tRNA in the peptidyl transferase reaction. Mol. Cell 20, 437–448 (2005)

    Article  CAS  PubMed  Google Scholar 

  54. Bieling, P., Beringer, M., Adio, S. & Rodnina, M. V. Peptide bond formation does not involve acid-base catalysis by ribosomal residues. Nature Struct. Mol. Biol. 13, 423–428 (2006)

    Article  CAS  Google Scholar 

  55. Schmeing, T. M., Huang, K. S., Strobel, S. A. & Steitz, T. A. An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Nature 438, 520–524 (2005)This paper shows that peptidyl-transferase activity involves an induced conformational change that opens the ester bond between the peptide and tRNA to nucleophilic attack.

    Article  CAS  PubMed  ADS  Google Scholar 

  56. Lang, K., Erlacher, M., Wilson, D. N., Micura, R. & Polacek, N. The role of 23S ribosomal RNA residue A2451 in peptide bond synthesis revealed by atomic mutagenesis. Chem. Biol. 15, 485–492 (2008)

    Article  CAS  PubMed  Google Scholar 

  57. Trobro, S. & Aqvist, J. Mechanism of peptide bond synthesis on the ribosome. Proc. Natl Acad. Sci. USA 102, 12395–12400 (2005)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  58. Sharma, P. K., Xiang, Y., Kato, M. & Warshel, A. What are the roles of substrate-assisted catalysis and proximity effects in peptide bond formation by the ribosome? Biochemistry 44, 11307–11314 (2005)

    Article  CAS  PubMed  Google Scholar 

  59. Nierhaus, K. H., Schulze, H. & Cooperman, B. S. Molecular mechanisms of the ribosomal peptidyltransferase center. Biochem. Int. 1, 185–192 (1980)

    CAS  Google Scholar 

  60. Hecht, S. M., Kozarich, J. W. & Schmidt, F. J. Isomeric phenylalanyl-tRNAs. Position of the aminoacyl moiety during protein biosynthesis. Proc. Natl Acad. Sci. USA 71, 4317–4321 (1974)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  61. Quiggle, K., Kumar, G., Ott, T. W., Ryu, E. K. & Chladek, S. Donor site of ribosomal peptidyltransferase: investigation of substrate specificity using 2′(3′)-O-(N-acylaminoacyl)dinucleoside phosphates as models of the 3′ terminus of N-acylaminoacyl transfer ribonucleic acid. Biochemistry 20, 3480–3485 (1981)

    Article  CAS  PubMed  Google Scholar 

  62. Dorner, S., Panuschka, C., Schmid, W. & Barta, A. Mononucleotide derivatives as ribosomal P-site substrates reveal an important contribution of the 2′-OH to activity. Nucleic Acids Res. 31, 6536–6542 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Weinger, J. S., Parnell, K. M., Dorner, S., Green, R. & Strobel, S. A. Substrate-assisted catalysis of peptide bond formation by the ribosome. Nature Struct. Mol. Biol. 11, 1101–1106 (2004)

    Article  CAS  Google Scholar 

  64. Koch, M., Huang, Y. & Sprinzl, M. Peptide-bond synthesis on the ribosome: no free vicinal hydroxy group required on the terminal ribose residue of peptidyl-tRNA. Angew. Chem. Int. Edn Engl. 47, 7242–7245 (2008)

    Article  CAS  Google Scholar 

  65. Bashan, A. et al. Structural basis of the ribosomal machinery for peptide bond formation, translocation, and nascent chain progression. Mol. Cell 11, 91–102 (2003)

    Article  CAS  PubMed  Google Scholar 

  66. Korostelev, A., Trakhanov, S., Laurberg, M. & Noller, H. F. Crystal structure of a 70S ribosome-tRNA complex reveals functional interactions and rearrangements. Cell 126, 1065–1077 (2006)

    Article  CAS  PubMed  Google Scholar 

  67. Wohlgemuth, I., Beringer, M. & Rodnina, M. V. Rapid peptide bond formation on isolated 50S ribosomal subunits. EMBO Rep. 7, 699–703 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Brunelle, J. L., Youngman, E. M., Sharma, D. & Green, R. The interaction between C75 of tRNA and the A loop of the ribosome stimulates peptidyl transferase activity. RNA 12, 33–39 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Voorhees, R. M., Weixlbaumer, A., Loakes, D., Kelley, A. C. & Ramakrishnan, V. Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome. Nature Struct. Mol. Biol. 16, 528–533 (2009)

    Article  CAS  Google Scholar 

  70. Bokov, K. & Steinberg, S. V. A hierarchical model for evolution of 23S ribosomal RNA. Nature 457, 977–980 (2009)

    Article  CAS  PubMed  ADS  Google Scholar 

  71. Wower, J., Hixson, S. S. & Zimmermann, R. A. Labeling the peptidyltransferase center of the Escherichia coli ribosome with photoreactive tRNA(Phe) derivatives containing azidoadenosine at the 3′ end of the acceptor arm: a model of the tRNA-ribosome complex. Proc. Natl Acad. Sci. USA 86, 5232–5236 (1989)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  72. Maguire, B. A., Beniaminov, A. D., Ramu, H., Mankin, A. S. & Zimmermann, R. A. A protein component at the heart of an RNA machine: the importance of protein l27 for the function of the bacterial ribosome. Mol. Cell 20, 427–435 (2005)

    Article  CAS  PubMed  Google Scholar 

  73. Trobro, S. & Aqvist, J. Role of ribosomal protein L27 in peptidyl transfer. Biochemistry 47, 4898–4906 (2008)

    Article  CAS  PubMed  Google Scholar 

  74. Moore, V. G., Atchison, R. E., Thomas, G., Moran, M. & Noller, H. F. Identification of a ribosomal protein essential for peptidyl transferase activity. Proc. Natl Acad. Sci. USA 72, 844–848 (1975)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  75. Kazemie, M. Binding of aminoacyl-tRNA to reconstituted subparticles of Escherichia coli large ribosomal subunits. Eur. J. Biochem. 67, 373–378 (1976)

    Article  CAS  PubMed  Google Scholar 

  76. Moazed, D. & Noller, H. F. Intermediate states in the movement of transfer RNA in the ribosome. Nature 342, 142–148 (1989)

    Article  CAS  PubMed  ADS  Google Scholar 

  77. Agirrezabala, X. et al. Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome. Mol. Cell 32, 190–197 (2008)This paper and ref. 78 show direct structural evidence for hybrid states following peptide-bond formation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Julián, P. et al. Structure of ratcheted ribosomes with tRNAs in hybrid states. Proc. Natl Acad. Sci. USA 105, 16924–16927 (2008)

    Article  PubMed  ADS  PubMed Central  Google Scholar 

  79. Frank, J. & Agrawal, R. K. A ratchet-like inter-subunit reorganization of the ribosome during translocation. Nature 406, 318–322 (2000)

    Article  CAS  PubMed  ADS  Google Scholar 

  80. Blanchard, S. C., Kim, H. D., Gonzalez, R. L., Puglisi, J. D. & Chu, S. tRNA dynamics on the ribosome during translation. Proc. Natl Acad. Sci. USA 101, 12893–12898 (2004)A ground-breaking paper on the use of single molecule techniques to study dynamics in the ribosome.

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  81. Cornish, P. V., Ermolenko, D. N., Noller, H. F. & Ha, T. Spontaneous intersubunit rotation in single ribosomes. Mol. Cell 30, 578–588 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ermolenko, D. N. et al. The antibiotic viomycin traps the ribosome in an intermediate state of translocation. Nature Struct. Mol. Biol. 14, 493–497 (2007)

    Article  CAS  Google Scholar 

  83. Fei, J., Kosuri, P., MacDougall, D. D. & Gonzalez, R. L. Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation. Mol. Cell 30, 348–359 (2008)

    Article  CAS  PubMed  Google Scholar 

  84. Munro, J. B., Altman, R. B., O’Connor, N. & Blanchard, S. C. Identification of two distinct hybrid state intermediates on the ribosome. Mol. Cell 25, 505–517 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pan, D., Kirillov, S. V. & Cooperman, B. S. Kinetically competent intermediates in the translocation step of protein synthesis. Mol. Cell 25, 519–529 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Schmeing, T. M., Moore, P. B. & Steitz, T. A. Structures of deacylated tRNA mimics bound to the E site of the large ribosomal subunit. RNA 9, 1345–1352 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Savelsbergh, A., Mohr, D., Wilden, B., Wintermeyer, W. & Rodnina, M. V. Stimulation of the GTPase activity of translation elongation factor G by ribosomal protein L7/12. J. Biol. Chem. 275, 890–894 (2000)

    Article  CAS  PubMed  Google Scholar 

  88. Lill, R., Robertson, J. M. & Wintermeyer, W. Binding of the 3′ terminus of tRNA to 23S rRNA in the ribosomal exit site actively promotes translocation. EMBO J. 8, 3933–3938 (1989)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Feinberg, J. S. & Joseph, S. Identification of molecular interactions between P-site tRNA and the ribosome essential for translocation. Proc. Natl Acad. Sci. USA 98, 11120–11125 (2001)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  90. Gavrilova, L. P., Koteliansky, V. E. & Spirin, A. S. Ribosomal protein S12 and ‘non-enzymatic’ translocation. FEBS Lett. 45, 324–328 (1974)

    Article  CAS  PubMed  Google Scholar 

  91. Cukras, A. R., Southworth, D. R., Brunelle, J. L., Culver, G. M. & Green, R. Ribosomal proteins S12 and S13 function as control elements for translocation of the mRNA:tRNA complex. Mol. Cell 12, 321–328 (2003)

    Article  CAS  PubMed  Google Scholar 

  92. Rodnina, M. V., Savelsbergh, A., Katunin, V. I. & Wintermeyer, W. Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome. Nature 385, 37–41 (1997)

    Article  CAS  PubMed  ADS  Google Scholar 

  93. Ævarsson, A. et al. Three-dimensional structure of the ribosomal translocase: elongation factor G from Thermus thermophilus. EMBO J. 13, 3669–3677 (1994)

    Article  PubMed  PubMed Central  Google Scholar 

  94. Czworkowski, J., Wang, J., Steitz, T. A. & Moore, P. B. The crystal structure of elongation factor G complexed with GDP, at 2.7 Å resolution. EMBO J. 13, 3661–3668 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Connell, S. R. et al. Structural basis for interaction of the ribosome with the switch regions of GTP-bound elongation factors. Mol. Cell 25, 751–764 (2007)

    Article  CAS  PubMed  Google Scholar 

  96. Hauryliuk, V. et al. The pretranslocation ribosome is targeted by GTP-bound EF-G in partially activated form. Proc. Natl Acad. Sci. USA 105, 15678–15683 (2008)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  97. Mohr, D., Wintermeyer, W. & Rodnina, M. V. GTPase activation of elongation factors Tu and G on the ribosome. Biochemistry 41, 12520–12528 (2002)

    Article  CAS  PubMed  Google Scholar 

  98. Ilag, L. L. et al. Heptameric (L12)6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria. Proc. Natl Acad. Sci. USA 102, 8192–8197 (2005)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  99. Harms, J. M. et al. Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin. Mol. Cell 30, 26–38 (2008)

    Article  CAS  PubMed  Google Scholar 

  100. Savelsbergh, A. et al. An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation. Mol. Cell 11, 1517–1523 (2003)

    Article  CAS  PubMed  Google Scholar 

  101. Studer, S. M., Feinberg, J. S. & Joseph, S. Rapid kinetic analysis of EF-G-dependent mRNA translocation in the ribosome. J. Mol. Biol. 327, 369–381 (2003)

    Article  CAS  PubMed  Google Scholar 

  102. Agrawal, R. K., Penczek, P., Grassucci, R. A. & Frank, J. Visualization of elongation factor G on the Escherichia coli 70S ribosome: the mechanism of translocation. Proc. Natl Acad. Sci. USA 95, 6134–6138 (1998)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  103. Stark, H., Rodnina, M. V., Wieden, H. J., van Heel, M. & Wintermeyer, W. Large-scale movement of elongation factor G and extensive conformational change of the ribosome during translocation. Cell 100, 301–309 (2000)

    Article  CAS  PubMed  Google Scholar 

  104. Takyar, S., Hickerson, R. P. & Noller, H. F. mRNA helicase activity of the ribosome. Cell 120, 49–58 (2005)

    Article  CAS  PubMed  Google Scholar 

  105. Gao, Y.-G. et al. The structure of the ribosome with elongation factor G trapped in the post-translocational state. Science 10.1126/science.1179709 (in the press)

  106. Frolova, L. Y. et al. Mutations in the highly conserved GGQ motif of class 1 polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis. RNA 5, 1014–1020 (1999)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Song, H. et al. The crystal structure of human eukaryotic release factor eRF1–mechanism of stop codon recognition and peptidyl-tRNA hydrolysis. Cell 100, 311–321 (2000)

    Article  CAS  PubMed  Google Scholar 

  108. Ito, K., Uno, M. & Nakamura, Y. A tripeptide ‘anticodon’ deciphers stop codons in messenger RNA. Nature 403, 680–684 (2000)

    Article  CAS  PubMed  ADS  Google Scholar 

  109. Vestergaard, B. et al. Bacterial polypeptide release factor RF2 is structurally distinct from eukaryotic eRF1. Mol. Cell (2001)

  110. Klaholz, B. P. et al. Structure of the Escherichia coli ribosomal termination complex with release factor 2. Nature 421, 90–94 (2003)

    Article  CAS  PubMed  ADS  Google Scholar 

  111. Rawat, U. B. et al. A cryo-electron microscopic study of ribosome-bound termination factor RF2. Nature 421, 87–90 (2003)

    Article  CAS  PubMed  ADS  Google Scholar 

  112. Petry, S. et al. Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon. Cell 123, 1255–1266 (2005)

    Article  CAS  PubMed  Google Scholar 

  113. Laurberg, M. et al. Structural basis for translation termination on the 70S ribosome. Nature 454, 852–857 (2008)This paper and ref. 114 provide insights into the recognition of stop codons by release factors.

    Article  CAS  PubMed  ADS  Google Scholar 

  114. Weixlbaumer, A. et al. Insights into translational termination from the structure of RF2 bound to the ribosome. Science 322, 953–956 (2008)

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  115. Korostelev, A. et al. Crystal structure of a translation termination complex formed with release factor RF2. Proc. Natl Acad. Sci. USA 105, 19684–19689 (2008)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  116. Youngman, E. M., He, S. L., Nikstad, L. J. & Green, R. Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release. Mol. Cell 28, 533–543 (2007)

    Article  CAS  PubMed  Google Scholar 

  117. Poole, E. S., Major, L. L., Mannering, S. A. & Tate, W. P. Translational termination in Escherichia coli: three bases following the stop codon crosslink to release factor 2 and affect the decoding efficiency of UGA-containing signals. Nucleic Acids Res. 26, 954–960 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Ito, K., Uno, M. & Nakamura, Y. Single amino acid substitution in prokaryote polypeptide release factor 2 permits it to terminate translation at all three stop codons. Proc. Natl Acad. Sci. USA 95, 8165–8169 (1998)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  119. Zaher, H. S. & Green, R. Quality control by the ribosome following peptide bond formation. Nature 457, 161–166 (2009)

    Article  CAS  PubMed  ADS  Google Scholar 

  120. Zavialov, A. V., Mora, L., Buckingham, R. H. & Ehrenberg, M. Release of peptide promoted by the GGQ motif of class 1 release factors regulates the GTPase activity of RF3. Mol. Cell 10, 789–798 (2002)

    Article  CAS  PubMed  Google Scholar 

  121. Shaw, J. J. & Green, R. Two distinct components of release factor function uncovered by nucleophile partitioning analysis. Mol. Cell 28, 458–467 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Mora, L. et al. The essential role of the invariant GGQ motif in the function and stability in vivo of bacterial release factors RF1 and RF2. Mol. Microbiol. 47, 267–275 (2003)

    Article  CAS  PubMed  Google Scholar 

  123. Dinçbas-Renqvist, V. et al. A post-translational modification in the GGQ motif of RF2 from Escherichia coli stimulates termination of translation. EMBO J. 19, 6900–6907 (2000)

    Article  PubMed  PubMed Central  Google Scholar 

  124. Zavialov, A. V., Buckingham, R. H. & Ehrenberg, M. A posttermination ribosomal complex is the guanine nucleotide exchange factor for peptide release factor rf3. Cell 107, 115–124 (2001)

    Article  CAS  PubMed  Google Scholar 

  125. Gao, H. et al. RF3 induces ribosomal conformational changes responsible for dissociation of class I release factors. Cell 129, 929–941 (2007)

    Article  CAS  PubMed  Google Scholar 

  126. Hirashima, A. & Kaji, A. Role of elongation factor G and a protein factor on the release of ribosomes from messenger ribonucleic acid. J. Biol. Chem. 248, 7580–7587 (1973)

    Article  CAS  PubMed  Google Scholar 

  127. Lancaster, L., Kiel, M. C., Kaji, A. & Noller, H. F. Orientation of ribosome recycling factor in the ribosome from directed hydroxyl radical probing. Cell 111, 129–140 (2002)

    Article  CAS  PubMed  Google Scholar 

  128. Agrawal, R. K. et al. Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: functional implications. Proc. Natl Acad. Sci. USA 101, 8900–8905 (2004)

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  129. Gao, N. et al. Mechanism for the disassembly of the posttermination complex inferred from cryo-EM studies. Mol. Cell 18, 663–674 (2005)

    Article  CAS  PubMed  Google Scholar 

  130. Wilson, D. N. et al. X-ray crystallography study on ribosome recycling: the mechanism of binding and action of RRF on the 50S ribosomal subunit. EMBO J. 24, 251–260 (2005)

    Article  CAS  PubMed  Google Scholar 

  131. Borovinskaya, M. A. et al. Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nature Struct. Mol. Biol. 14, 727–732 (2007)

    Article  CAS  Google Scholar 

  132. Weixlbaumer, A. et al. Crystal structure of the ribosome recycling factor bound to the ribosome. Nature Struct. Mol. Biol. 14, 733–737 (2007)

    Article  CAS  Google Scholar 

  133. Heurgué-Hamard, V. et al. Ribosome release factor RF4 and termination factor RF3 are involved in dissociation of peptidyl-tRNA from the ribosome. EMBO J. 17, 808–816 (1998)

    Article  PubMed  PubMed Central  Google Scholar 

  134. Rao, A. R. & Varshney, U. Specific interaction between the ribosome recycling factor and the elongation factor G from Mycobacterium tuberculosis mediates peptidyl-tRNA release and ribosome recycling in Escherichia coli. EMBO J. 20, 2977–2986 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank R. Voorhees for a critical reading of this manuscript, and J. Frank and X. Aggirrezabala for providing coordinates of a hybrid state complex. Work in V.R.’s laboratory is supported by the Medical Research Council (UK), the Wellcome Trust, the Louis-Jeantet Foundation and the Agouron Institute. T.M.S. was supported by fellowships from the Human Frontiers Science Program and Emmanuel College, Cambridge. Part of this review was written when V.R. was a G. N. Ramachandran Visiting Professor at the Indian Institute of Science, Bangalore, where he thanks U. Varshney for his hospitality and useful discussions.

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Schmeing, T., Ramakrishnan, V. What recent ribosome structures have revealed about the mechanism of translation. Nature 461, 1234–1242 (2009). https://doi.org/10.1038/nature08403

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