Role of Elongation Factors in Steering the Ribosomal Elongation Cycle

  • Knud H. Nierhaus
  • Francisco Triana


The detection and characterization of the third transfer RNA (tRNA)-binding site on the ribosome, the E site, in addition to the classical A and P sites has led to the allosteric three-site model (ref. 1 and references therein), which has provided fresh impetus for discussion of and insights into the ribosomal elongation mechanism. It allows, for example, for the first time the identification of a common inhibition mechanism for aminoglycoside antibiotics,2 which do not exert their antibiotic activity by inducing misreading3 as previously assumed. The implications of the allosteric three-site model for the selection of the correct aminoacyl-tRNA and for the role of the elongation factors will be surveyed here. We start with a brief description of the main features of the allosteric three-site model, then address the problem of recognition involved in the selection of cognate aminoacyl-tRNAs and describe a surprising solution to this problem, which might be related to such fundamental structural features as the two-subunit nature of all ribosomes. We close the chapter with a first attempt to describe the mechanism of both elongation factors.


Elongation Factor Allosteric Transition Activation Energy Barrier Elongation Cycle Recognition Area 
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.


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  1. 1.
    Gnirke, A., Geigenmüller, U., Rheinberger, H.-J., and Nierhaus, K. H., 1989, The allosteric three-site model for the ribosomal elongation cycle: Analysis with a heteropolymeric mRNA, J. Biol. Chem. 264:7291–7301.PubMedGoogle Scholar
  2. 2.
    Hausner, T.-P., Geigenmüller, U., and Nierhaus, K. H., 1988, The allosteric three-site model for the ribosomal elongation cycle: New insights into the inhibition mechanisms of aminoglycosides, thiostrepton, and viomycin, J. Biol. Chem. 263:13103–13111.PubMedGoogle Scholar
  3. 3.
    Fast, R., Eberhard, T. H., Ruusala, R., and Kurland, C. G., 1987, Does streptomycin cause an error catastrophe? Biochimie 69:131–136.PubMedCrossRefGoogle Scholar
  4. 4.
    Nierhaus, K. H., 1990, The allosteric three-site model for the ribosomal elongation cycle: Features and future, Biochemistry 29:4997–5008.PubMedCrossRefGoogle Scholar
  5. 5.
    Rheinberger, H.-J., and Nierhaus, K. H., 1986, Allosteric interactions between the ribosomal transfer RNA-binding sites A and E, J. Biol. Chem. 261:9133–9139.PubMedGoogle Scholar
  6. 6.
    Rheinberger, H.-J., Sternbach, H., and Nierhaus, K. H., 1986, Codon-anticodon interaction at the ribosomal E site, J. Biol. Chem. 261:9140–9143.PubMedGoogle Scholar
  7. 7.
    Rheinberger, H.-J., and Nierhaus, K. H., 1986, Adjacent codon-anticodon interactions of both tRNAs present at the ribosomal A and P or P and E sites, FEBS Lett. 204:97–99.PubMedCrossRefGoogle Scholar
  8. 8.
    Wurmbach, P., and Nierhaus, K. H., 1979, Codon-anticodon interaction at the ribosomal P (peptidyl-tRNA) site, Proc. Natl. Acad. Sci. USA 76:2143–2147.PubMedCrossRefGoogle Scholar
  9. 9.
    Lührmann, R., Eckhard, H., and Stöffler, G., 1979, Codon-anticodon interaction at the ribosomal peptidyl site, Nature 280:423–425.PubMedCrossRefGoogle Scholar
  10. 10.
    Peters, M., and Yarus, M., 1979, Transfer RNA selection at the ribosomal A and P sites, J. Mol. Biol. 134:471–491.PubMedCrossRefGoogle Scholar
  11. 11.
    Geigenmüller, U., and Nierhaus, K. H., 1990, Significance of the third tRNA binding site, the E site, on E. coli ribosomes for the accuracy of translation: An occupied E site prevents the binding of non-cognate aminoacyl-tRNA to the A site, EMBO J. 9:4527–4533.PubMedGoogle Scholar
  12. 12.
    Schilling-Bartetzko, S., Bartetzko, A., and Nierhaus, K. H., 1992, Kinetic and thermodynamic parameters for tRNA binding to the ribosome and for the translocation reaction, J. Biol. Chem. 267:4703–4712.PubMedGoogle Scholar
  13. 13.
    Moazed, D., and Noller, H. F., 1989, Intermediate states in the movement of transfer RNA in the ribosome, Nature 342:142–148.PubMedCrossRefGoogle Scholar
  14. 14.
    Rheinberger, H.-J., and Nierhaus, K. H., 1987, The ribosomal E site at low Mg2+: Coordinate inactivation of ribosomal functions at Mg2+ concentrations below 10 mM and its prevention by polyamines, J. Biomol. Struct. Dynam. 5:435–446.CrossRefGoogle Scholar
  15. 15.
    Quigley, G. J., Wang, A. H. J., Seeman, N. C., Suddath, F. L., Rich, A., Sussman, J. L., and Kim, S. H., 1975, Hydrogen bonding in yeast phenylalanine transfer RNA, Proc. Natl. Acad. Sci. USA 72:4866–4870.PubMedCrossRefGoogle Scholar
  16. 16.
    Schilling-Bartetzko, S., Franceschi, F. J., and Nierhaus, K. H., 1992, Apparent association constants of tRNAs for the ribosomal A, P and E sites, J. Biol. Chem. 267:4633–4702.Google Scholar
  17. 17.
    Komine, Y., Adachi, T., Inokuchi, H., and Ozeki, H., 1990, Genomic organization and physical mapping of the transfer RNA genes in Escherichia coli K12, J. Mol. Biol. 212:579–598.PubMedCrossRefGoogle Scholar
  18. 18.
    Potapov, A. P., 1982, A stereospecific mechanism for the aminoacyl-tRNA selection at the ribosome, FEBS Lett. 146:5–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Andersson, S. G. E., Buckingham, R. H., and Kurland, C. G., 1984, Does codon composition influence ribosome function? EMBO J. 3:91–94.PubMedGoogle Scholar
  20. 20.
    Kurland, C. G., 1980, On the accuracy of elongation, in: Ribosomes (G. Chambliss, G. R. Craven, J. Davies, K. Davis, L. Kahan, and M. Nomura, eds.), pp. 597–614, University Park Press, Baltimore.Google Scholar
  21. 21.
    Hopfield, J. J., and Yamane, T., 1980, The fidelity of protein synthesis, in: Ribosomes (G. Chambliss, G. R. Craven, J. Davies, K. Davis, L. Kahan, and M. Nomura, eds.), pp. 585–596, University Park Press, Baltimore.Google Scholar
  22. 22.
    Nierhaus, K. H., 1982, Structure, assembly, and function of ribosomes, in: Current Topics in Microbiology and Immunology ,Volume 97 (W. Henle, P. H. HofSchneider, H. Koprowski, F. Melchers, R. Rott, H. G. Schweiger, and P. K. Vogt, eds.), pp. 81–155, Spinger-Verlag, Berlin.CrossRefGoogle Scholar
  23. 23.
    Gnirke, A., and Nierhaus, K. H., 1986, tRNA binding sites on the subunits of Escherichia coli ribosomes, J. Biol. Chem. 261:14506–14514.PubMedGoogle Scholar
  24. 24.
    Endo, Y., and Wool, I. G., 1982, The site of action of α-sarcin on eukaryotic ribosomes: The sequence at the α-sarcin cleavage site in 28S ribosomal ribonucleic acid, J. Biol. Chem. 257: 9054–9060.PubMedGoogle Scholar
  25. 25.
    Hausner, T.-P., Atmadja, J., and Nierhaus, K. H., 1987, Evidence that the G2661 region of 23S rRNA is located at the ribosomal binding sites of both elongation factors, Biochimie 69:911–923.PubMedCrossRefGoogle Scholar
  26. 26.
    Wool, I. G., 1984, The mechanism of action of the cytotoxic nuclease α-sarcin and its use to analyse ribosome structure, Trends Biochem. Sci. 9:14–17.CrossRefGoogle Scholar
  27. 27.
    Endo, Y., Huber, P. W., and Wool, I. G., 1983, The nuclease activity of the cytotoxin α-sarcin: The characteristics of the enzymatic activity of α-sarcin with ribosomes and ribonucleic acids as substrates, J. Biol. Chem. 258:2662–2667.PubMedGoogle Scholar
  28. 28.
    Miller, D. L., 1972, Elongation factors EF-Tu and EF-G interact at related sites on ribosomes, Proc. Natl. Acad. Sci. USA 69:753–755.Google Scholar
  29. 29.
    Richter, D., 1973, Competition between the elongation factors 1 and 2, and phenylalanyl transfer ribonucleic acid for the ribosomal binding sites in a polypeptide-synthesizing system from the brain, J. Biol. Chem. 248:2853–2857.PubMedGoogle Scholar
  30. 30.
    Moazed, D., Robertson, J. M., and Noller, H. F., 1988, Interaction of elongation factors EF-G and EF-Tu with a conserved loop in 23S RNA, Nature 334:362–364.PubMedCrossRefGoogle Scholar
  31. 31.
    Twardowski, T., and Nierhaus, K. H., 1993, The α-sarcin stem-loop structure of 23S rRNA: Hybridization of antisense probes provokes drastic effects on the large ribosomal subunit, submitted.Google Scholar
  32. 32.
    Gavrilova, L. P., Perminova, I. N., and Spirin, A. S., 1981, Elongation factor Tu can reduce translation errors in poly(U)-directed cell-free systems, J. Mol. Biol. 149:69–78.PubMedCrossRefGoogle Scholar
  33. 33.
    Freier, S. M., Kierzek, R., Jaeger, J. A., Sugimoto, N., Caruthers, M. H., Neilson, T., and Turner, D. H., 1986, Improved free-energy parameters for predictions of RNA duplex stability, Proc. Natl. Acad. Sci. USA 83:9373–9377.PubMedCrossRefGoogle Scholar
  34. 34.
    Jaeger, J. A., Turner, D. H., and Zuker, M., 1989, Improved predictions of secondary structures for RNA, Proc. Natl. Acad. Sci. USA 86:7706–7710.PubMedCrossRefGoogle Scholar
  35. 35.
    Gutell, R. R., Schnare, M. N., and Gray, M. W., 1990, A compilation of large subunit (23S-like) ribosomal RNA sequences presented in a secondary structure format, Nucleic Acids Res. 18:2319– 2330.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Knud H. Nierhaus
    • 1
  • Francisco Triana
    • 1
  1. 1.Max-Planck-Institut für Molekulare GenetikBerlin 33Germany

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