Ribosomes pp 303-319 | Cite as

Dynamic views of ribosome function: Energy landscapes and ensembles

  • P. C. Whitford
  • R. B. Altman
  • P. Geggier
  • D. S. Terry
  • J. B. Munro
  • J. N. Onuchic
  • C. M. T. Spahn
  • K. Y. Sanbonmatsu
  • S. C. Blanchard

Abstract

Single-molecule fluorescence resonance energy transfer (smFRET) (reviewed in Munro et al., 2009) and cryo-electron microscopy (cryo-EM) investigations (Frank and Spahn, 2006; Spahn and Penczek, 2009; Fischer et al., 2010) of the translation apparatus reveal the ribosome’s propensity to undergo large-scale fluctuations in conformation during function. Progress in these areas, building upon achievements in high-resolution structure determination of ribosomal subunits and functional complexes of the ribosome (Yusupov et al., 2001; Wekselman et al., 2009: Zhang et al., 2009; Gao et al., 2009; Demeshkina et al., 2010; Stanley et al., 2010), combined with an ever increasing breadth of computational modeling, simulation (Sanbonmatsu and Tung, 2007; Whitford et al., 2010a), and bioinformatics approaches (Roberts et al., 2008; Alexander et al., 2010), offers the potential to further broaden our understanding of the dynamic nature of the ribosome and translation components during protein synthesis. The large fluctuations observed by single-molecule studies, and the multitude of conformations reported by cryo-EM, make it clear that each “state” of the ribosome is in fact an ensemble of structurally similar configurations that are localized to a particular minimum on the free-energy landscape.

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References

  1. Agirrezabala X, Lei J, Brunelle JL, Ortiz-Meoz RF, Green R, Frank J (2008) Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome. Mol Cell 32: 190–197PubMedGoogle Scholar
  2. Besseová I, Réblová K, Leontis NB, Sponer J (2010) Molecular dynamics simulations sugg est that RNA three-way junctions can act as flexible RNA structural elements in the ribosome. Nuc Acid Res 38:6247–6264; DOI:101093/nar/gkq414Google Scholar
  3. Best RB, Hummer G (2010) Coordinate-dependent diffusion in protein folding. Proc Natl Acad Sci USA 19: 1088–1093Google Scholar
  4. Blanchard SC, Gonzalez RL, Kim HD, Chu S, Puglisi JD (2004a) tRNA selection and kinetic proofreading in translation. Nat Struct Mol Bio 11: 1008–1014Google Scholar
  5. Blanchard SC, Kim HD, Gonzalez RL Jr, Puglisi JD, Chu S (2004b) tRNA dynamics on the ribosome during translation. Proc Natl Acad Sci USA 101: 12893–12898PubMedGoogle Scholar
  6. Blanchard SC (2009) Single-molecule observations of ribosome function. Curr Op Struct Bio 19: 103–109Google Scholar
  7. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J Comp Chem 4: 187–217Google Scholar
  8. Bryngelson JD, Wolynes PG (1989) Intermediates and barrier crossing in a random energy model (with applications to protein folding). J Phys Chem 93: 6902–6915Google Scholar
  9. Cho SS, Levy Y, Wolynes PG (2006) P versus Q: structural reaction coordinates capture protein folding on smooth landscapes. Proc Natl Acad Sci USA 103: 586: 591PubMedGoogle Scholar
  10. Cornish PV, Ermolenko DN, Noller HF, Ha T (2008) Spontaneous intersubunit rotation in single ribosomes. Mol Cell 30: 578–588PubMedGoogle Scholar
  11. Cornish P, Ermolenko D, Staple D, Hoang L, Hickerson R, Noller H, Ha T (2009) Following movement of the L1 stalk between three functional states in single ribosomes. Proc Natl Acad Sci USA 106: 2571–2576PubMedGoogle Scholar
  12. Das P, Moll M, Stamati H, Kavraki LE, Clementi C (2006) Low-dimensional, free-energy landscapes of protein-folding reactions by nonlinear dimensionality reduction. Proc Natl Acad Sci USA 103: 9885–9890PubMedGoogle Scholar
  13. Demeshkina N, Jenner L, Yusupova G, Yusupov M (2010) Interactions of the ribosome with mRNA and tRNA. Curr Op Struct Biol 20: 325–332Google Scholar
  14. Dorner S, Brunelle JL, Sharma D, Green R (2006) The hybrid state of tRNA binding is an authentic translation elongation intermediate. Nat Struct Mol Biol 13: 234–241PubMedGoogle Scholar
  15. Dudko OK, Hummer G, Szabo A (2006) Intrinsic rates and activation free energies from single-molecule pulling experiments. Phys Rev Lett 96: 108101PubMedGoogle Scholar
  16. Faradjian AK, Elber R (2004) Computing time scales from reaction coordinates by milestoning. J Chem Phys 120: 10880–10889PubMedGoogle Scholar
  17. Fei J, Kosuri P, MacDougall DD, Gonzalez RL Jr. (2008) Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation. Mol Cell 30: 348–359PubMedGoogle Scholar
  18. Fei J, Bronson JE, Hofman JM, Srinivas RL, Wiggins CH, Gonzalez RL (2009) Allosteric collaboration between elongation factor G and the ribosomal L1 stalk directs tRNA movement during translation. Proc Natl Acad Sci USA 106: 15702–15707PubMedGoogle Scholar
  19. Fischer N, Konevega AL, Wintermeyer W, Rodnina MV, Stark H (2010) Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy. Nature 466: 329–333PubMedGoogle Scholar
  20. Fluitt A, Pienaar E, Viljoen H (2007) Ribosome kinetics and aa-tRNA competition determine rate and fidelity of peptide synthesis. Comp Bio Chem 31: 335–346Google Scholar
  21. Frank J, Sengupta J, Gao H, Li W, Valle M, Zavialov A, Ehrenberg M (2005) The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer. FEBS Lett 579: 959–962PubMedGoogle Scholar
  22. Frank J, Spahn CM (2006) The ribosome and the mechanism of protein synthesis. Rep Prog Phys 69: 1383–1417Google Scholar
  23. Frank J, Gao H, Sengupta J, Gao N, Taylor DJ (2007) The process of mRNA-tRNA translocation. Proc Natl Acad Sci USA 104: 19671–19678PubMedGoogle Scholar
  24. Frauenfelder H, Petsko GA, Tsernoglou D (1979) Temperature-dependent x-ray-diffraction as a probe of protein structural dynamics. Nature 280: 558–563PubMedGoogle Scholar
  25. Frauenfelder H, Sligar SG, Wolynes PG (1991) The energy landscapes of motions of proteins. Science 254: 1598–1603PubMedGoogle Scholar
  26. Gao Y-G, Selmer M, Dunham CM, Weixlbaumer A, Kelley AC, Ramakrishnan V (2009) The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326: 694–699PubMedGoogle Scholar
  27. Garcia AE (1992) Large-amplitude nonlinear motions in proteins. Phys Rev Lett 68: 2696–2699PubMedGoogle Scholar
  28. Garcia AE, Onuchic JN (2003) Folding a protein in a computer: An atomic description of the folding/unfolding of protein A. Proc Natl Acad Sci USA 13898–13903Google Scholar
  29. Garcia AE, Krumhansl JA, Frauenfelder H (1997) Variations on a theme by Debye and Waller: From simple crystals to proteins. Prot Struct Func Gen 29: 153–160Google Scholar
  30. Gavrilova LP, Kostiashkina OE, Koteliansky VE, Rutkevitch NM, Spirin AS (1976) Factor-free (“non-enzymic”) and factor-dependent systems of translation of polyuridylic acid by Escherichia coli ribosomes. J Mol Biol 101: 537–552PubMedGoogle Scholar
  31. Geggier P, Dave R, Feldman MB, Terry DS, Altman RB, Munro JB, Blanchard SC (2010) Conformational sampling of amino-acyl-tRNA during selection on the ribosome. J Mol Biol 399: 576–595; DOI:101016/j. jmb.2010.04038PubMedGoogle Scholar
  32. Gesteland RF, Atkins JF (1996) Recoding: dynamic reprogramming of translation. Annu Rev Biochem 65: 741–768PubMedGoogle Scholar
  33. Gromadski KB, Rodnina MV (2004) Kinetic determinants of high-fidelity tRNA discrimination on the ribosome. Mol Cell 13: 191–200PubMedGoogle Scholar
  34. Hyeon C, Onuchic JN (2007) Mechanical control of the directional stepping dynamics of the kinesin motor. Proc Natl Acad Sci USA 104: 17382–17387PubMedGoogle Scholar
  35. Hopfield JJ (1974) Kinetic proofreading: A new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci USA 71: 4135–4139PubMedGoogle Scholar
  36. Johansson M, Bouakaz E, Lovmar M, Ehrenberg M (2008) The kinetics of ribosomal peptidyl transfer revisited. Mol Cell 30: 589–598PubMedGoogle Scholar
  37. Julian P, Konevega AL, Scheres SH, Lazaro M, Gil D, Wintermeyer W, Rodnina MV, Valle M (2008) Structure of ratcheted ribosomes with tRNAs in hybrid states. Proc Natl Acad Sci USA 105: 16924–16927PubMedGoogle Scholar
  38. Klaholz BP, Myasnikov AG, van Heel M (2004) Visualization of release factor 3 on the ribosome during termination of protein synthesis. Nature 427: 862–865PubMedGoogle Scholar
  39. Klepeis JL, Lindorff-Larsen K, Dror RO, Shaw DE (2009) Long-timescale molecular dynamics simulations of protein structure and function. Curr Opin Struct Biol 19: 120–127PubMedGoogle Scholar
  40. Komatsuzuki T, Hoshino K, Matsunaga Y, Rylance GJ, Johnston RL, Wales DJ (2005) How many dimensions are required to approximate the potential energy landscape of a model protein? J Chem Phys 122: 084714Google Scholar
  41. Korostelev A, Noller HF (2007) Analysis of structural dynamics in the ribosome byTLS crystallographic refinement. J Mol Biol 373: 1058–1070PubMedGoogle Scholar
  42. Korostelev A, Asahara H, Lancaster L, Laurberg M, Hirschi A, Zhu J, Trakhanov S, Scott WG, Noller HF (2008) Crystal structure of a translation termination complex formed with release factor RF2. Proc Natl Acad Sci USA 105: 19684–19689PubMedGoogle Scholar
  43. Landau LD, Lifshitz EM, Pitaevskii LP (1984) Electrodynamics of continuous media, 2nd ed. Reed Educational and Professional Publishing, OxfordGoogle Scholar
  44. Lee T-H, Blanchard SC, Kim HD, Puglisi JD, Chu S (2007) The role of fluctuations in tRNA selection by the ribosome. Proc Natl Acad Sci USA 104: 13661–13665PubMedGoogle Scholar
  45. Leopold PE, Montal M, Onuchic JN (1992) Protein folding funnels-A kinetic approach to the sequence structure relationship. Proc Natl Acad Sci USA 89: 8721–8725PubMedGoogle Scholar
  46. Lu Q, Wang J (2009) Kinetics and statistical distributions of single-molecule conformational dynamics. J Phys Chem B 113: 1517–1521PubMedGoogle Scholar
  47. Marshall RA, Dorywalska M, Puglisi JD (2008) Irreversible chemical steps control intersubunit dynamics during translation. Proc Natl Acad Sci USA 105: 15364–15369PubMedGoogle Scholar
  48. Miyashita O, Onuchic JN, Wolynes PG (2003) Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins. Proc Natl Acad Sci USA 100: 12570–12575PubMedGoogle Scholar
  49. Munro JB, Altman RB, O’Connor, Blanchard SC (2007) Identification of two distinct hybrid-state intermediates on the ribosome. Mol Cell 25: 505–517PubMedGoogle Scholar
  50. Munro JB, Sanbonmatsu KY, Spahn CMT, Blanchard SC (2009) Navigating the ribosome’s metastable energy landscape. Trends Biochem Sci 34: 390–400PubMedGoogle Scholar
  51. Munro JB, Altman RB, Tung C-S, Sanbonmatsu KY, Blanchard SC (2010a) A fast dynamic mode of EF-G-bound ribosome. EMBO J 29: 770–781PubMedGoogle Scholar
  52. Munro JB, Altman RB, Tung C-S, Cate JDH, Sanbonmatsu KY, Blanchard SC (2010b) Spontaneous formation of the unlocked state of the ribosome is a multistep process. Proc Natl Acad Sci USA 107: 709–714PubMedGoogle Scholar
  53. Nettels D, Gopich IV, Hoffman A, Schuler B (2007) Ultrafast dynamics of protein collapse from single-molecule photon statistics. Proc Natl Acad Sci USA 104: 2655–2660PubMedGoogle Scholar
  54. Nettels D, Hoffmann A, Schuler B (2008) Unfolded protein and peptide dynamics investigated with single-molecule FRET and correlation spectroscopy from picoseconds to seconds. J Phys Chem B 112: 6137–6146PubMedGoogle Scholar
  55. Nymeyer H, Socci ND, Onuchic JN (2000) Landscape approaches for determining the ensemble of folding transition states: Success and failures hinge on the degree of frustration. Proc Natl Acad Sci USA 97: 634–639PubMedGoogle Scholar
  56. Oliveira RJ, Whitford PC, Chahine J, Wang J, Onuchic JN, Leite VBP (2010) Exploring the origin of non-monotonic complex behavior and the effects of non-native interactions on the diffusive properties of protein folding. Biophys J (in press)Google Scholar
  57. Onuchic JN, Wolynes PG (1993) Energy landscapes, glass transitions, and chemical reaction dynamics in biomolecular or solvent environment. J Chem Phys 98: 2218–2224Google Scholar
  58. Onuchic JN, Nymeyer H, Garcia AE, Chahine J, Socci ND (2000) The energy landscape theory of protein folding: Insights into folding mechanisms and scenarios. Adv Protein Chem 53: 87–152PubMedGoogle Scholar
  59. Onuchic JN, Kobayashi C, Miyashita O, Jennings P, Baldridge KK (2006) Exploring biomolecular machines: energy landscape control of biological reactions. Philos Trans Royal Soc 361: 1439–1443Google Scholar
  60. Orzechowski M, Tama F (2008) Flexible fitting of high-resolution X-ray structures into cryo-electron microscopy maps using biased molecular dynamics simulations. Biophys J 95: 5692–5705PubMedGoogle Scholar
  61. Pape T, Wintermeyer W, Rodnina M (1999) Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome. EMBO J 18: 3800–3807PubMedGoogle Scholar
  62. Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE III, DeBolt S, Ferguson D, Seibel G, Kollman P (1995) AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comp Phys Commun 91: 1–41Google Scholar
  63. Penczek PA, Frank J, Spahn CMT (2006) A method of focused classification, based on the bootstrap 3D variance analysis, and its applications to EF-G-dependent translocation. 154: 184–194Google Scholar
  64. Peng C, Zhang L, Head-Gordon T (2010) Instantaneous normal modes as an unforced reaction coordinate for protein conformational transitions. Biophys J 98: 2356–2364PubMedGoogle Scholar
  65. Pérez A, Marchán I, Svozil D, Sponer J, Cheatham TE III, Laughton CA, Orozco M (2007) Refinement of the AMBER force field for nucleic acids: Improving the description of alpha/gamma conformers. Biophys J 92: 3817–3829PubMedGoogle Scholar
  66. Pincus DL, Cho SS, Hyeon C, Thirumalai D (2009) Minimal models for proteins and RNA: From folding to function. In: Molecular biology of protein folding, Vol 84, pp 203–250. Elsevier Academic, San Diego, CAGoogle Scholar
  67. Ratje AH, Loerke J, Mikolajka A, Brünner M, Hildebrand PW, Starosta A, Doenhoefer A, Connel SR, Fucini P, Mielke T, Whitford PC, Onuchic JN, Yu Y, Sanbonmatsu KY, Hartmann RK, Penczek PA, Wilson DN, Spahn CMT (2010) Head swivel on the ribosome facilitates translocation via intra-subunit tRNA hybrid sites. Nature 468: 713–716 (under review)PubMedGoogle Scholar
  68. Roberts E, Sethi A, Montoya J, Woese CR, Luthey-Schulten Z (2008) Molecular signatures of ribosomal evolution. Proc Natl Acad Sci USA 105: 13953–13958PubMedGoogle Scholar
  69. Roberts RW, Eargle J, Luthey-Schulten Z (2010) Experimental and computational determination of tRNA dynamics. FEBS Lett 584: 376–386Google Scholar
  70. Rodnina MV, Wintermeyer W (2001) Fidelity of aminoacyl-tRNA selection on the ribosome: Kinetic and structural mechanisms. Annu Rev Biochem 70: 415–435PubMedGoogle Scholar
  71. Sanbonmatsu KY (2006a) Energy landscape of the ribosomal decoding center. Biochimie 88: 1053–1059PubMedGoogle Scholar
  72. Sanbonmatsu KY (2006b) Alignment/misalignment hypothesis for tRNA selection by the ribosome. Biochimie 88: 1075–1089PubMedGoogle Scholar
  73. Sanbonmatsu KY, Tung C-S (2007) High performance computing in biology: Multimillion atom simulations of nanoscale systems. J Struct Bio 157: 470–480Google Scholar
  74. Schmeing TM, Voorhees RM, Kelley AC, Gao Y-G, Murphy FV, Weir JR, Ramakrishnan V (2009) The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science 326: 688–694PubMedGoogle Scholar
  75. Schuette J-C, Murphy FC, Kelly AC, Weir JR, Geisebrecht J, Connell SR, Loerke J, Mielke T, Zhang W, Penczek PA, Ramakrishnan V, Spahn CMT (2009) GTPase activation of elongation factor EF-Tu by the ribosome during decoding. EMBO J 28: 1–11Google Scholar
  76. Schuler B, Lipman EA, Eaton WA (2002) Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy. Nature 419: 743–748PubMedGoogle Scholar
  77. Sievers A, Beringer M, Rodnina MV, Wolfenden R (2004) The ribosome as an entropy trap. Proc Natl Acad Sci USA 101: 7897–7901PubMedGoogle Scholar
  78. Spahn CMT, Penczek PA (2009) Exploring conformational modes of macromolecular assemblies by multiparticle cryo-EM. Curr Opin Struct Biol 19: 623–631PubMedGoogle Scholar
  79. Spirin AS (2009) The ribosome as a conveying thermal ratchet machine. J Biol Chem 284: 21103–21119PubMedGoogle Scholar
  80. Stanley RE, Blaha G, Grodzicki RL, Strickler MD, Steitz TA (2010) The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome. Nat Struct Mol Biol 17: 289–293PubMedGoogle Scholar
  81. Tama F, Valle M, Frank J, Brooks CL III (2003) Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy. Proc Natl Acad Sci USA 100: 9319–9323PubMedGoogle Scholar
  82. Tang J, Kang S-G, Saven, JG, Gai F (2009) Characterization of the cofactor-induced folding mechanism of a zinc-binding peptide using computationally designed mutants. J Mol Biol 389: 90–102PubMedGoogle Scholar
  83. Trabuco LG, Harrison CB, Schreiner E, Schulten K (2010) Recognition of the regulatory nascent chain TnaC by the ribosome. Structure 18: 627–637PubMedGoogle Scholar
  84. Thirumalai D, Hyeon C (2005) RNA and protein folding: Common themes and variations. Biochem 44: 4957–4970Google Scholar
  85. Thirumalai D, O’Brien EP, Morrison G, Hyeon C (2010) Theoretical perspectives on protein folding. Annu Rev Biophys 39: 159–183PubMedGoogle Scholar
  86. Trylska J, Tozzini V, McCammon JA (2005) Exploring global motions and correlations in the ribosome. Biophys J 89: 1455–1463PubMedGoogle Scholar
  87. Vaiana AC, Sanbonmatsu KY (2009) Stochastic gating and drug-ribosome interactions. J Mol Biol 386: 648–661PubMedGoogle Scholar
  88. Vanheel M, Frank J (1981) Use of multivariate statistics in analyzing the images of biological macromolecules. Ultramicroscopy 6: 187–194Google Scholar
  89. Villa E, Sengupta J, Trabuco L, LeBarron J, Baxter WT, Shaikh TR, Grassucci RA, Nissen P, Ehrenberg M, Schulten K, Frank J (2009) Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. Proc Natl Acad Sci USA 106: 1063–1068PubMedGoogle Scholar
  90. Wales DJ (1984) Energy Landscapes: Applications to clusters, biomolecules and glasses. Cambridge University Press, Cam bridgeGoogle Scholar
  91. Wang J (2003) Statistics, pathways and dynamics of single molecule protein folding. J Chem Phys 118: 952–958Google Scholar
  92. Wang Y, Rader AJ, Bahar I, Jernigan RL (2004) Global ribosome motions revealed with elastic network model. J Struct Biol 147: 302–314PubMedGoogle Scholar
  93. Weber G (1975) Energetics of ligand binding to proteins. Adv Protein Chem 29: 1–83PubMedGoogle Scholar
  94. Wekselmen I, Davidovich C, Agmon I, Zimmerman E, Rozenberg H, Bashan A, Birisio R, Yonath A (2009) Ribosome’s mode of function: myths, facts and recent results. J Pept Sci 15: 122–130Google Scholar
  95. Whitford PC, Miyashita O, Levy Y, Onuchic JN (2007) Conformational transistions of adenylate kinase: switching by cracking. J Mol Biol 366: 1661–1671PubMedGoogle Scholar
  96. Whitford PC, Noel JK, Gosavi S, Schug A, Sanbonmatsu KY, Onuchic JN (2009a) An all-atom structure-based potential for proteins: Bridging minimal models with all-atom empirical forcefields. Prot Struc Func Bioinfo 75: 430–441Google Scholar
  97. Whitford PC, Schug A, Saunders J, Hennelly SP, Onuchic JN, Sanbonmatsu KY (2009b) Nonlocal helix formation is key to understanding S-Adenosylmethionine-1 riboswitch function. Biophys J 96: L7–L9PubMedGoogle Scholar
  98. Whitford PC, Geggier P, Altman RB, Blanchard SC, Onuchic JN, Sanbonmatsu KY (2010a) Accommodation of aminoacyl-tRNA into the ribosome involves reversible excursions along multiple pathways. RNA 16: 1196–1204; DOI: 101261/rna.2 035410PubMedGoogle Scholar
  99. Whitford PC, Onuchic JN, Sanbonmatsu KY (2010b) Connecting energy landscapes with experimental rates for aminoacyl-tRNA accommodation in the ribosome J Amer Chem Soc 132: 13170–13171 (submitted)Google Scholar
  100. Williams ML, Landel RF, Ferry JD (1955) Mechanical properties of substances of high molecular weight. 19. The temperature dependence of relaxation mechanisms in amorphous polymers and other glass-forming liquids. J Amer Chem Soc 77: 3701–3707Google Scholar
  101. Wong V, Case DA (2008) Evaluating rotational diffusion from protein MD simulations. J Phys Chem B 112: 6013–6024.PubMedGoogle Scholar
  102. Yang S, Roux B (2008) Src kinase conformational activation: thermodynamics, pathways, and mechanisms. PLOS Comp Biol 4: e1000047Google Scholar
  103. Yusupov MM, Yusupova GZ, Baucom A, Leiberman K, Earnest TN, Cate JH, Noller HF (2001) Crystal structure of the ribosome at 5.5 Å. Science 292: 883–896PubMedGoogle Scholar
  104. Zhang G, Feyunin I, Miekley O, Valleriani A, Moura A, Ignatova Z (2010) Global and local depletion of ternary complex limits translation elongation. Nuc Acid Res 38: 4778–4787Google Scholar
  105. Zhang W, Dunkle A, Cate JHD (2009) Structures of the ribosome in intermediate states of ratcheting. Science 325: 1014–1017PubMedGoogle Scholar
  106. Zwanzig R (1988) Diffusion in a rough potential. Proc Natl Acad Sci USA 85: 2029–2030PubMedGoogle Scholar

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© Springer-Verlag/Wien 2011

Authors and Affiliations

  • P. C. Whitford
  • R. B. Altman
  • P. Geggier
  • D. S. Terry
  • J. B. Munro
  • J. N. Onuchic
  • C. M. T. Spahn
  • K. Y. Sanbonmatsu
  • S. C. Blanchard

There are no affiliations available

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