How Do Nascent Proteins Emerge from the Ribosome?

  • Ada Yonath
Conference paper
Part of the NATO Science for Peace and Security Series B: Physics and Biophysics book series (NAPSB)


The ribosome is the universal cellular “factory” for producing proteins by translating the genetic code. These highly efficient polymerases posses spectacular architecture and inherent mobility, allowing their smooth performance in decoding the genetic information as well as the formation of peptide bonds, elongation of the newly born proteins and their protection (for review see [45] ChemBioChem 10:63–72, 2009).


Tunnel Wall Large Ribosomal Subunit Peptide Bond Formation Nascent Protein Exit Tunnel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Thanks are due to all members of the ribosome groups at the Weizmann Institute and the Max Planck Society for their experimental efforts and illuminating discussion. Support was provided by the US National Inst. of Health (GM34360), the German Ministry for Science and Technology (BMBF 05-641EA), GIF 853–2004, Human Frontier Science Program (HFSP) RGP0076/2003 and the Kimmelman Center for Macromolecular Assemblies. AY holds the Martin and Helen Kimmel Professorial Chair. X-ray diffraction data were collected the EMBL and MPG beam lines at DESY; F1/CHESS, Cornell University, SSRL/Stanford University, ESRF/EMBL, Grenoble, BL26/PF/KEK, Japan and 19ID&23ID/APS/Argonne National Laboratory.


  1. 1.
    Agmon I, Bashan A, Zarivach R, Yonath A (2005) Symmetry at the active site of the ribosome: structural and functional implications. Biol Chem 386:833–844CrossRefGoogle Scholar
  2. 2.
    Agmon I (2009) The dimeric proto-ribosome: structural details and possible implications on the origin of life. Int J Mol Sci 10:2921–2934CrossRefGoogle Scholar
  3. 3.
    Agmon I, Bashan A, Yonath A (2006) On ribosome conservation and evolution Isr. J Ecol Evol 52:359–379CrossRefGoogle Scholar
  4. 4.
    Amit M, Berisio R, Baram D, Harms J, Bashan A, Yonath A (2005) A crevice adjoining the ribosome tunnel: hints for cotranslational folding. FEBS Lett 579:3207–3213CrossRefGoogle Scholar
  5. 5.
    Ban N, Nissen P, Hansen J, Moore PB, Steitz TA (2000) The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science 289:905–920ADSCrossRefGoogle Scholar
  6. 6.
    Baram D, Pyetan E, Sittner A, Auerbach-Nevo T, Bashan A, Yonath A (2005) Structure of trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action. Proc Natl Acad Sci USA 102:12017–12022ADSCrossRefGoogle Scholar
  7. 7.
    Bashan A, Agmon I, Zarivach R, Schluenzen F, Harms J, Berisio R, Bartels H, Franceschi F, Auerbach T, Hansen HA, Kossoy E, Kessler M, Yonath A (2003) Structural basis of the ribosomal machinery for peptide bond formation, translocation, and nascent chain progression. Mol Cell 11:91–102CrossRefGoogle Scholar
  8. 8.
    Belousoff MJ, Davidovich C, Zimmerman E, Caspi Y, Wekselman I, Rozenszajn L, Shapira T, Sade-Falk O, Taha L, Bashan A, Weiss MS, Yonath A (2010) Ancient machinery embedded in the contemporary ribosome. Biochem Soc Trans 38:422–427CrossRefGoogle Scholar
  9. 9.
    Berisio R, Schluenzen F, Harms J, Bashan A, Auerbach T, Baram D, Yonath A. (2003) Structural insight into the role of the ribosomal tunnel in cellular regulation. Nat Struct Biol 10:366–370CrossRefGoogle Scholar
  10. 10.
    Bhushan S, Gartmann M, Halic M, Armachel J, Jaraschl A, Mielke T, Berninghausen O, Wilson DN, Beckmann R (2010) Helical segments of the nascent polypeptide chains visualized within distinct regions of the ribosomal exit tunnel. Nat Struct Mol Biol 17:313–317CrossRefGoogle Scholar
  11. 11.
    Bokov K, Steinberg SV (2009) A hierarchical model for evolution of 23 S ribosomal RNA. Nature 457:977–980ADSCrossRefGoogle Scholar
  12. 12.
    Bommakanti AS, Lindahl L, Zengel JM (2008) Mutation from guanine to adenine in 25 S rRNA at the position equivalent to E. coli A2058 does not confer erythromycin sensitivity in Sacchromyces cerevisae. RNA 14:460–464CrossRefGoogle Scholar
  13. 13.
    Chiba S, Lamsa A, Pogliano K (2009) A ribosome-nascent chain sensor of membrane protein biogenesis in Bacillus subtilis. EMBO J 28:3461–3475CrossRefGoogle Scholar
  14. 14.
    Crowley KS, Reinhart GD, Johnson AE (1993) The signal sequence moves through a ribosomal tunnel into a noncytoplasmic aqueous environment at the ER membrane early in translocation. Cell 73:1101–1105CrossRefGoogle Scholar
  15. 15.
    Cruz-Vera LR, Gong M, Yanofsky C (2006) Changes produced by bound tryptophan in the ribosome peptidyl transferase center in response to TnaC, a nascent leader peptide. Proc Natl Acad Sci USA 103:3598–3603ADSCrossRefGoogle Scholar
  16. 16.
    Davidovich C, Belousoff M, Bashan A, Yonath A (2009) The evolving ribosome: from non-coded peptide bond formation to sophisticated translation machinery. Res Microbiol 160:487–492CrossRefGoogle Scholar
  17. 17.
    Frank J, Zhu J, Penczek P, Li Y, Srivastava S, Verschoor A, Radermacher M, Grassucci R, Lata RK, Agrawal RK (1995) A model of protein synthesis based on cryo-electron microscopy of the E. coli ribosome. Nature 376:441–444ADSCrossRefGoogle Scholar
  18. 18.
    Gong F, Yanofsky C (2002) Instruction of translating ribosome by nascent Peptide. Science 297:1864–1867ADSCrossRefGoogle Scholar
  19. 19.
    Harms J, Schluenzen F, Zarivach R, Bashan A, Gat S, Agmon I, Bartels H, Franceschi F, Yonath A (2001) High resolution structure of the large ribosomal subunit from a mesophilic eubacterium. Cell 107:679–688CrossRefGoogle Scholar
  20. 20.
    Ito K, Chiba S, Pogliano K (2010) Divergent stalling sequences sense and control cellular physiology. Biochem Biophys Res Commun 39:1–6CrossRefGoogle Scholar
  21. 21.
    Johnson AE, Jensen RE (2004) Barreling through the membrane. Nat Struct Mol Biol 11:113–114CrossRefGoogle Scholar
  22. 22.
    Kaiser CM, Chang HC, Agashe VR, Lakshmipathy SK, Etchells SA, Hayer-Hartl M, Hartl FU, Barral JM (2006) Real-time observation of trigger factor function on translating ribosomes. Nature 444:455–460ADSCrossRefGoogle Scholar
  23. 23.
    Malkin L, Rich A (1967) Partial resistance of nascent polypeptide chains to proteolytic digestion due to ribosomal shielding. J Mol Biol 26:329–346CrossRefGoogle Scholar
  24. 24.
    Mankin AS (2006) Nascent peptide in the “birth canal” of the ribosome. Trends Biochem Sci 31:3–11CrossRefGoogle Scholar
  25. 25.
    Martinez-Hackert E, Hendrickson WA (2009) Promiscuous substrate recognition in folding and assembly activities of the trigger factor chaperone. Cell 138:923–934CrossRefGoogle Scholar
  26. 26.
    Milligan RA, Unwin PN (1986) Location of exit channel for nascent protein in 80 S ribosome. Nature 319:693–695ADSCrossRefGoogle Scholar
  27. 27.
    Moore PB (1988) The ribosome returns. Nature 331:223–227ADSCrossRefGoogle Scholar
  28. 28.
    Nakatogawa H, Ito K (2002) The ribosomal exit tunnel functions as a discriminating gate. Cell 108:629–636CrossRefGoogle Scholar
  29. 29.
    Nakatogawa H, Murakami A, Ito K (2004) Control of SecA and SecM translation by protein secretion. Curr Opin Microbiol 7:145–150CrossRefGoogle Scholar
  30. 30.
    Nakatogawa H, Ito K (2004) Intraribosomal regulation of expression and fate of proteins. Chembiochem 5:48–51CrossRefGoogle Scholar
  31. 31.
    Nissen P, Hansen J, Ban N, Moore PB, Steitz TA (2000) The structural basis of ribosome activity in peptide bond synthesis. Science 289:920–930ADSCrossRefGoogle Scholar
  32. 32.
    Ryabova LA, Selivanova OM, Baranov VI, Vasiliev VD, Spirin AS (1988) Does the channel for nascent peptide exist inside the ribosome? Immune electron microscopy study. FEBS Lett 226:255–260CrossRefGoogle Scholar
  33. 33.
    Sabatini DD, Blobel G (1970) Controlled proteolysis of nascent polypeptides in rat liver cell fractions. II. Location of the polypeptides in rough microsomes. J Cell Biol 45:146–157CrossRefGoogle Scholar
  34. 34.
    Schluenzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F (2001) Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413:814–821ADSCrossRefGoogle Scholar
  35. 35.
    Schluenzen F, Wilson DN, Tian P, Harms JM, McInnes SJ, Hansen HA, Albrecht R, Buerger J, Wilbanks SM, Fucini P (2005) The binding mode of the trigger factor on the ribosome: implications for protein folding and SRP interaction. Structure (Camb) 13:1685–1694CrossRefGoogle Scholar
  36. 36.
    Stark H, Mueller F, Orlova EV, Schatz M, Dube P, Erdemir T, Zemlin F, Brimacombe R, van Heel M (1995) The 70S Escherichia coli ribosome at 23A resolution: fitting the ribosomal RNA, Structure 3:815–821CrossRefGoogle Scholar
  37. 37.
    Tanner DR, Cariello DA, Woolstenhulme CJ, Broadbent MA, Buskirk AR (2009) Genetic identification of nascent peptides that induce ribosome stalling. J Biol Chem 284:34809–34818CrossRefGoogle Scholar
  38. 38.
    Tu LW, Deutsch C (2010) A folding zone in the ribosomal exit tunnel for Kv1.3 Helix formation. J Mol Biol 396:1346–1360CrossRefGoogle Scholar
  39. 39.
    Walter P, Johnson AE (1994) Signal sequence recognition and protein targeting to the endoplasmic reticulum membrane. Annu Rev Cell Biol 10:87–119CrossRefGoogle Scholar
  40. 40.
    Woolhead CA, Johnson AE, Bernstein HD (2006) Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. Mol Cell 22:587–598CrossRefGoogle Scholar
  41. 41.
    Woolhead CA, McCormick PJ, Johnson AE (2004) Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell 116:725–736CrossRefGoogle Scholar
  42. 42.
    Yap MN, Bernstein HD (2009) The plasticity of a translation arrest motif yields insights into nascent polypeptide recognition inside the ribosome tunnel. Mol Cell 34:201–211CrossRefGoogle Scholar
  43. 43.
    Yonath A, Leonard KR, Wittmann HG (1987) A tunnel in the large ribosomal subunit revealed by three-dimensional image reconstruction. Science 236:813–816ADSCrossRefGoogle Scholar
  44. 44.
    Zaman S, Fitzpatrick M, Lindahl L, Zengel J (2007) Novel mutations in ribosomal proteins L4 and L22 that confer erythromycin resistance in E. coli. Mol Microbiol 66:1039–1050CrossRefGoogle Scholar
  45. 45.
    Zimmerman E, Yonath A (2009) Biological implications of the ribosome’s stunning stereochemistry. Chembiochem 10:63–72CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Structural BiologyWeizmann InstituteRehovotIsrael

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