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A structural understanding of the dynamic ribosome machine

Key Points

  • The ribosome consists of two ribonucleoprotein subunits. The small subunit mediates the interactions between the anticodons of the tRNAs and the codons in the mRNA that they are translating to determine the order of amino acids in the protein being synthesized. The large subunit contains the peptidyl-transferase centre (PTC), which catalyses the formation of peptide bonds in the growing polypeptide.

  • An incoming tRNA is delivered to the A site in complex with elongation factor (EF)-Tu–GTP. Correct codon–anticodon pairing activates the GTPase centre of the ribosome that causes hydrolysis of GTP and EF-Tu to release the aminoacyl end of the tRNA.

  • Watson–Crick base pairs are formed between the mRNA and the P-site tRNA, which positions the peptidyl-tRNA, but unlike the A site, the rRNA does not make interactions with the codon–anticodon base-paired triplets that 'check' the accuracy of this interaction.

  • Binding of tRNA induces conformational changes in ribosomal (r)RNA that optimally orientates the peptidyl-tRNA and aminoacyl-tRNA for the peptidyl-transferase reaction to occur, which involves the transfer of the peptide chain onto the A-site tRNA. The ribosome must then shift in the 3′ mRNA direction so that it can decode the next mRNA codon.

  • Translocation of the tRNAs and mRNA is facilitated by binding of the GTPase EF-G, which causes the P-site deacylated tRNA to move to the E site and the A-site peptidyl-tRNA to move to the P site on GTP hydrolysis. The ribosome is then ready for the next round of elongation.

  • When a stop codon in the mRNA reaches the A site of the ribosome at the end of the elongation phase of protein synthesis, translocational release factors catalyse the hydrolysis and release of the ester-linked polypeptide on the P-site tRNA.


Ribosomes, which are central to protein synthesis and convert transcribed mRNAs into polypeptide chains, have been the focus of structural and biochemical studies for more than 50 years. The structure of its larger subunit revealed that the ribosome is a ribozyme with RNA at the heart of its enzymatic activity that catalyses peptide bond formation. Numerous initiation, elongation and release factors ensure that protein synthesis occurs progressively and with high specificity. In the past few years, high-resolution structures have provided molecular snapshots of different intermediates in ribosome-mediated translation in atomic detail. Together, these studies have revolutionized our understanding of the mechanism of protein synthesis.

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Figure 1: An overview of ribosomal structure and mRNA translation.
Figure 2: Recognition of codon–anticodon interactions by the ribosome.
Figure 3: P-site–tRNA interactions in the ribosome.
Figure 4: Substrate-induced rearrangements in the peptidyl-transferase centre promote peptide chain formation and suppress hydrolysis.
Figure 5: Different interactions of the tRNA with the E site across kingdoms.
Figure 6: Space-filling models of the polypeptide exit tunnel.
Figure 7: An overview of termination of translation.

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  1. Palade, G. E. A small particulate component of the cytoplasm. J. Biophys. Biochem. Cytol. 1, 59–68 (1955).

    Article  CAS  Google Scholar 

  2. Watson, J. D. Involvement of RNA in the synthesis of proteins. Science 140, 17–26 (1963).

    Article  CAS  Google Scholar 

  3. Lake, J. A. Ribosomal structure determined by electron microscopy of E. coli small subunits, large subunits and monomeric ribosomes. J. Mol. Biol. 105, 131–159 (1976).

    Article  CAS  Google Scholar 

  4. Schuwirth, B. S. et al. Structures of the bacterial ribosome at 3.5 Å resolution. Science 310, 827–834 (2005). Presents the first complete atomic structure of the 70S ribosome from E. coli derived from a high-resolution map, but without bound substrates.

    Article  CAS  Google Scholar 

  5. Selmer, M. et al. Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313, 1935–1942 (2006). The most complete and accurate structure of the 70S ribosome published to date also has bound mRNA, as well as tRNAs at the A site (partial), P site and E site.

    Article  CAS  Google Scholar 

  6. Korostelev, A., Trakhanov, S., Laurberg, M. & Noller, H. F. Crystal structure of a 70S ribosome–tRNA complex reveals functional interactions and rearrangements. Cell 126, 1066–1077 (2006).

    Article  Google Scholar 

  7. Ogle, J. M. et al. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902 (2001). The structure of the 30S subunit with mRNA and an anticodon stem-loop RNA mimic of tRNA shows how decoding occurs in the A site.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. 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). Shows that the binding of an appropriate A-site substrate to the 50S subunit complex with a P-site substrate induces an active site conformational change that is essential for catalysis.

    Article  CAS  Google Scholar 

  10. 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  Google Scholar 

  11. Schmeing, T. M. et al. A pre-translocational intermediate in protein synthesis observed in crystals of enzymatically active 50S subunits. Nature Struct. Biol. 9, 225–230 (2002).

    CAS  PubMed  Google Scholar 

  12. Green, R. & Noller, H. F. Ribosomes and translation. Annu. Rev. Biochem. 66, 679–716 (1997).

    Article  CAS  Google Scholar 

  13. Nissen, P., Ippolito, J. A., Ban, N., Moore, P. B. & Steitz, T. A. RNA tertiary interactions in the large ribosomal subunit: the A-minor motif. Proc. Natl Acad. Sci. USA 98, 4899–4903 (2001).

    Article  CAS  Google Scholar 

  14. Ogle, J. M., Murphy, F. V. I., 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Valle, M. et al. Cryo-EM reveals an active role for aminoacyl tRNA in the accommodation process. EMBO J. 21, 3557–3567 (2002).

    Article  CAS  Google Scholar 

  17. 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 

  18. 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  Google Scholar 

  19. Berk, V., Zhang, W., Pai, R. D. & Cate, J. H. D. Structural basis for mRNA and tRNA positioning on the ribosome. Proc. Natl Acad. Sci. USA 103, 15830–15834 (2006).

    Article  CAS  Google Scholar 

  20. Maguire, B. A., Benaminov, 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  Google Scholar 

  21. Moore, P. B. & Steitz, T. A. The structural basis of large ribosomal subunit function. Annu. Rev. Biochem. 72, 813–850 (2003).

    Article  CAS  Google Scholar 

  22. 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  Google Scholar 

  23. Koshland, D. E. Mechanism of transfer enzymes. In The Enzymes (Boyer, P. D., Lardy, H. & Myrback, K., eds) 305–346 (Academic Press, New York, 1959).

    Google Scholar 

  24. Bennett, W. S. & Steitz, T. A. Glucose-induced conformational change in yeast hexokinase. Proc. Natl Acad. Sci. USA 75, 4848–4852 (1976).

    Article  Google Scholar 

  25. Beringer, M. & Rodnina, M. V. The ribosomal peptidyl transferase. Mol. Cell 26, 311–321 (2007).

    Article  CAS  Google Scholar 

  26. Caskey, C. T., Beaudet, A. L., Scolnick, E. M. & Rosman, M. Hydrolysis of fMet-tRNA by peptidyl transferase. Proc. Natl Acad. Sci. USA 68, 3163–3167 (1971).

    Article  CAS  Google Scholar 

  27. Pape, T., Wintermeyer, W. & Rodnina, M. V. Conformational switch in the decoding region of 16S rRNA during aminoacyl-tRNA selection on the ribosome. Nature Struct. Biol. 7, 104–107 (2000).

    Article  CAS  Google Scholar 

  28. Paige, M. I. & Jencks, W. P. Entropic contributions to rate acceleration in enzymatic and intramolecular reactions and the chelate effect. Proc. Natl Acad. Sci. USA 68, 1678–1683 (1971).

    Article  Google Scholar 

  29. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. 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. Biol. 11, 1101–1106 (2004). Biochemical demonstration of the large contribution of the 2′ hydroxyl group of A76 of the P-site substrate to peptide bond formation.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  34. Valle, M., Zavialov, A., Sengupta, J., Rawat, U., Ehrenberg, M. & Frank, J. Locking and unlocking of ribosomal motions. Cell 114, 123–134 (2003).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  37. Rodnina, M., Savelsbergh, A., Katunin, V. I. & Wintermeyer, W. Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome. Nature 385, 37–41 (1979).

    Article  Google Scholar 

  38. Frank, J. & Agrawal, R. K. A ratchet-like inter-subunit reorganization of the ribosome during translocation. Nature 406, 318–322 (2000). The important rotation of the small subunit relative to the large subunit on EFG–GTP binding is shown in this cryo-EM study.

    Article  CAS  Google Scholar 

  39. 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). The highest-resolution cryo-EM structure of the 70S ribosome with bound EFG gives insights into the mechanism of its function in translocation.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  41. Schroeder, S., Blaha, G., Tirado-Rives, J., Steitz, T. A. & Moore, P. B. The structures of antibiotics bound to the E-site region of the 50S ribosomal subunit of Haloarcula marismortui; 13-deoxytedanolide and girodazole. J. Mol. Biol. 367, 1471–1479 (2007).

    Article  CAS  Google Scholar 

  42. Milligan, R. A. & Unwin, P. N. In vitro crystallization of ribosomes from chick embryos. J. Cell Biol. 95, 648–653 (1982).

    Article  CAS  Google Scholar 

  43. 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  Google Scholar 

  44. Gabashvili, I. S. et al. The polypeptide tunnel system in the ribosome and its gating in erythromycin mutants of L4 and L22. Mol. Cell 8, 181–188 (2001).

    Article  CAS  Google Scholar 

  45. Voss, N. R., Gerstein, M., Steitz, T. A. & Moore, P. B. The geometry of the ribosomal exit tunnel. J. Mol. Biol. 360, 893–906 (2006).

    Article  CAS  Google Scholar 

  46. Gilbert, R. J. et al. Three dimensional structures of translating ribosomes by cryo-EM. Mol. Cell 14, 57–66 (2004).

    Article  CAS  Google Scholar 

  47. Malkin, L. I. & Rich, A. Partial resistance of nascent polypeptide chains to proteolytic digestion due to ribosomal shielding. J. Mol. Biol. 26, 329–346 (1967).

    Article  CAS  Google Scholar 

  48. Klein, D. J., Moore, P. B. & Steitz, T. A. The roles of ribosomal proteins in the structure, assembly and evolution of the large ribosomal subunit. J. Mol. Biol. 340, 141–177 (2004).

    Article  CAS  Google Scholar 

  49. Ferhtz, L. et al. Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins. Nature 431, 590–596 (2004).

    Article  Google Scholar 

  50. Schlünzen, F. et al. The binding mode of the trigger factor in the ribosome: implications for protein folding and SRP interaction. Structure 13, 1685–1694 (2005).

    Article  Google Scholar 

  51. 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, 1256–1266 (2005).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  53. 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 

  54. 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 

  55. van den Berg, B. et al. X-ray structure of a protein-conducting channel. Nature 427, 36–44 (2004).

    Article  CAS  Google Scholar 

  56. Mitra, K. et al. Structure of the E. coli protein-conducting channel bound to a translating ribosome. Nature 438, 318–324 (2005).

    Article  CAS  Google Scholar 

  57. Dever, T. E. Gene-specific regulation by general translation factors. Cell 108, 545–556 (2002).

    Article  CAS  Google Scholar 

  58. Sonenberg, N. & Dever, T. E. Eukaryotic translation initiation factors and regulators. Curr. Opin. Struct. Biol. 13, 56–63 (2003).

    Article  CAS  Google Scholar 

  59. Simonovic, M. & Steitz, T. A. Cross-crystal averaging reveals that the structure of the peptidyl-transferase center is the same in the 70S ribosome and 50S subunit. Proc. Natl Acad. Sci. USA. 105, 500–505 (2008).

    Article  CAS  Google Scholar 

  60. Brunnelle, J. L. et al. The interaction between C75 of tRNA and the A loop of the ribosome stimulates peptidyl transferase activity. RNA 12, 33–39 (2006).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  62. Janosi, L., Shimizu, I., Kaji, A. Ribosome recycling factor (ribosome releasing factor) is essential for bacterial growth. Proc. Natl Acad. Sci. USA 91, 4249–4253 (1994).

    Article  CAS  Google Scholar 

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A unit that is composed of three nucleotides in the tRNA that are complementary to and recognize the three bases of the codon on the mRNA.

A site

The site on the ribosome that binds aminoacyl-tRNA.


A tRNA attached to an amino acid, which is ester linked to the sugar of the 3′ nucleotide.

P site

The site on the ribosome that binds peptidyl-tRNA.


A tRNA with the peptide being synthesized linked to the 3′ nucleotide.

70S ribosome

The complete prokaryotic ribosome particle, which is composed of the small (30S) subunit and large (50S) subunit.

Ribosomal RNA

(rRNA). A type of RNA that is synthesized in the nucleolus by RNA polymerase I. Approximately 65% of a ribosome is composed of rRNA.

Peptidyl-transferase centre

(PTC). The active site of the ribosome where peptide bond formation occurs.

E site

The site on the ribosome that binds the deacylated tRNA before it leaves the ribosome.


Elongation factor Tu (temperature unstable), known as EF-1 in other kingdoms, delivers the aminoacyl tRNA to the ribosome in a codon-specific manner.


Elongation factor G (GTPase), known as EF-2 in other kingdoms, binds to the ribosome and promotes tRNA and mRNA translocation powered by GTP hydrolysis.

Stop codon

A codon that codes for the end of the message that is recognized by the release factor.

Release factor

(RF). A protein factor that recognizes a stop codon in mRNA and catalyses the deacylation of the peptidyl-tRNA.

GTPase centre

The region of the ribosome 50S subunit that includes the sarcin–ricin RNA and stimulates the GTPase activity of elongation factors.


The structure that is formed when a self-complementary nucleic acid sequence forms a duplex joined by a loop.

Type I A–minor interaction

A specific hydrogen-bonding interaction between an A base and a G–C base pair through the minor groove of duplex RNA.

Watson–Crick base pairs

The complementary hydrogen bond between bases A and T (or U) and G and C that form duplex nucleic acids.

Type II A–minor interaction

A second type of specific hydrogen bonding between an A base and a G–C base pair through the minor groove of duplex RNA.

Wobble base pair

A non-Watson–Crick base pair such as G–U.

D stem

One of the three stem-loops of the tRNA cloverleaf that stacks on the anticodon stem, forming one arm of the tRNA molecule.


A ribosome is classified as a ribozyme (ribonucleic acid enzyme) because its active site is composed of RNA.

Nucleophilic attack

A reaction whereby an electron-rich atom (such as nitrogen) attacks an electropositive group.

Trigger factor

A prokaryotic protein that binds to the ribosome tunnel exit and assists in nascent polypeptide folding.

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Steitz, T. A structural understanding of the dynamic ribosome machine. Nat Rev Mol Cell Biol 9, 242–253 (2008).

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