Cited by 57RNA and protein synthesis mechanismsEvolution and Genetic DynamicsProtein Structure and Dynamics

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

The Ribosome as an Optimal Decoder: A Lesson in Molecular Recognition

Open access

Abstract

The ribosome is a complex molecular machine that, in order to synthesize proteins, has to decode mRNAs by pairing their codons with matching tRNAs. Decoding is a major determinant of fitness and requires accurate and fast selection of correct tRNAs among many similar competitors. However, it is unclear whether the modern ribosome, and in particular its large conformational changes during decoding, are the outcome of adaptation to its task as a decoder or the result of other constraints. Here, we derive the energy landscape that provides optimal discrimination between competing substrates and thereby optimal tRNA decoding. We show that the measured landscape of the prokaryotic ribosome is sculpted in this way. This model suggests that conformational changes of the ribosome and tRNA during decoding are means to obtain an optimal decoder. Our analysis puts forward a generic mechanism that may be utilized broadly by molecular recognition systems.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.cell.2013.03.032

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. Bashan, 2008, Correlating ribosome function with high-resolution structures, Trends Microbiol., 16, 326, 10.1016/j.tim.2008.05.001 · DOI
  2. Blanchard, 2004, tRNA selection and kinetic proofreading in translation, Nat. Struct. Mol. Biol., 11, 1008, 10.1038/nsmb831 · DOI · Paper page
  3. Bouadloun, 1983, Codon-specific missense errors in vivo, EMBO J., 2, 1351, 10.1002/j.1460-2075.1983.tb01591.x · DOI
  4. Demeshkina, 2012, A new understanding of the decoding principle on the ribosome, Nature, 484, 256, 10.1038/nature10913 · DOI
  5. De Vlaminck, 2012, Mechanism of homology recognition in DNA recombination from dual-molecule experiments, Mol. Cell, 46, 616, 10.1016/j.molcel.2012.03.029 · DOI
  6. Ehrenberg, 1984, Costs of accuracy determined by a maximal growth rate constraint, Q. Rev. Biophys., 17, 45, 10.1017/S0033583500005254 · DOI
  7. Ferreiro, 2011, On the role of frustration in the energy landscapes of allosteric proteins, Proc. Natl. Acad. Sci. USA, 108, 3499, 10.1073/pnas.1018980108 · DOI
  8. Frank, 2005, The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer, FEBS Lett., 579, 959, 10.1016/j.febslet.2004.10.105 · DOI
  9. Gromadski, 2004, Kinetic determinants of high-fidelity tRNA discrimination on the ribosome, Mol. Cell, 13, 191, 10.1016/S1097-2765(04)00005-X · DOI
  10. Gromadski, 2004, Streptomycin interferes with conformational coupling between codon recognition and GTPase activation on the ribosome, Nat. Struct. Mol. Biol., 11, 316, 10.1038/nsmb742 · DOI
  11. Gromadski, 2006, A uniform response to mismatches in codon-anticodon complexes ensures ribosomal fidelity, Mol. Cell, 21, 369, 10.1016/j.molcel.2005.12.018 · DOI
  12. Herschlag, 1988, The role of induced fit and conformational changes of enzymes in specificity and catalysis, Bioorg. Chem., 16, 62, 10.1016/0045-2068(88)90038-7 · DOI
  13. Hopfield, 1974, Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity, Proc. Natl. Acad. Sci. USA, 71, 4135, 10.1073/pnas.71.10.4135 · DOI · Paper page
  14. Johansson, 2008, Rate and accuracy of bacterial protein synthesis revisited, Curr. Opin. Microbiol., 11, 141, 10.1016/j.mib.2008.02.015 · DOI
  15. Johansson, 2012, Genetic code translation displays a linear trade-off between efficiency and accuracy of tRNA selection, Proc. Natl. Acad. Sci. USA, 109, 131, 10.1073/pnas.1116480109 · DOI
  16. Kurland, 1992, Translational accuracy and the fitness of bacteria, Annu. Rev. Genet., 26, 29, 10.1146/annurev.ge.26.120192.000333 · DOI · Paper page
  17. Lee, 2007, The role of fluctuations in tRNA selection by the ribosome, Proc. Natl. Acad. Sci. USA, 104, 13661, 10.1073/pnas.0705988104 · DOI
  18. Marshall, 2008, Translation at the single-molecule level, Annu. Rev. Biochem., 77, 177, 10.1146/annurev.biochem.77.070606.101431 · DOI
  19. Mikkola, 1988, Media dependence of translational mutant phenotype, FEMS Microbiol. Lett., 56, 265, 10.1111/j.1574-6968.1988.tb03189.x · DOI
  20. Munro, 2009, Navigating the ribosome’s metastable energy landscape, Trends Biochem. Sci., 34, 390, 10.1016/j.tibs.2009.04.004 · DOI
  21. Ninio, 1975, Kinetic amplification of enzyme discrimination, Biochimie, 57, 587, 10.1016/S0300-9084(75)80139-8 · DOI
  22. Ninio, 2006, Multiple stages in codon-anticodon recognition: double-trigger mechanisms and geometric constraints, Biochimie, 88, 963, 10.1016/j.biochi.2006.06.002 · DOI
  23. Ogle, 2005, Structural insights into translational fidelity, Annu. Rev. Biochem., 74, 129, 10.1146/annurev.biochem.74.061903.155440 · DOI
  24. Ogle, 2001, Recognition of cognate transfer RNA by the 30S ribosomal subunit, Science, 292, 897, 10.1126/science.1060612 · DOI · Paper page
  25. Ogle, 2002, Selection of tRNA by the ribosome requires a transition from an open to a closed form, Cell, 111, 721, 10.1016/S0092-8674(02)01086-3 · DOI · Paper page
  26. Pape, 1999, Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome, EMBO J., 18, 3800, 10.1093/emboj/18.13.3800 · DOI
  27. Post, 1995, Reexamination of induced fit as a determinant of substrate specificity in enzymatic reactions, Biochemistry, 34, 15881, 10.1021/bi00049a001 · DOI
  28. Rodnina, 2001, Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms, Annu. Rev. Biochem., 70, 415, 10.1146/annurev.biochem.70.1.415 · DOI
  29. Savir, 2007, Conformational proofreading: the impact of conformational changes on the specificity of molecular recognition, PLoS ONE, 2, e468, 10.1371/journal.pone.0000468 · DOI
  30. Savir, 2008, Optimal design of a molecular recognizer: molecular recognition as a Bayesian signal detection problem, IEEE J. Sel. Topics Signal Process., 2, 390, 10.1109/JSTSP.2008.923859 · DOI
  31. Savir, 2009, Molecular recognition as an information channel: the role of conformational changes, Information Sciences and Systems, CISS, 2009, 835
  32. Savir, 2010, RecA-mediated homology search as a nearly optimal signal detection system, Mol. Cell, 40, 388, 10.1016/j.molcel.2010.10.020 · DOI
  33. Schmeing, 2009, What recent ribosome structures have revealed about the mechanism of translation, Nature, 461, 1234, 10.1038/nature08403 · DOI
  34. Schmeing, 2009, The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA, Science, 326, 688, 10.1126/science.1179700 · DOI
  35. Schuette, 2009, GTPase activation of elongation factor EF-Tu by the ribosome during decoding, EMBO J., 28, 755, 10.1038/emboj.2009.26 · DOI
  36. Schug, 2010, From protein folding to protein function and biomolecular binding by energy landscape theory, Curr. Opin. Pharmacol., 10, 709, 10.1016/j.coph.2010.09.012 · DOI
  37. Villa, 2009, Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis, Proc. Natl. Acad. Sci. USA, 106, 1063, 10.1073/pnas.0811370106 · DOI
  38. Whitford, 2010, Accommodation of aminoacyl-tRNA into the ribosome involves reversible excursions along multiple pathways, RNA, 16, 1196, 10.1261/rna.2035410 · DOI
  39. Whitford, 2010, Connecting energy landscapes with experimental rates for aminoacyl-tRNA accommodation in the ribosome, J. Am. Chem. Soc., 132, 13170, 10.1021/ja1061399 · DOI
  40. Whitford, 2011, Excited states of ribosome translocation revealed through integrative molecular modeling, Proc. Natl. Acad. Sci. USA, 108, 18943, 10.1073/pnas.1108363108 · DOI
  41. Yarus, 2003, A twisted tRNA intermediate sets the threshold for decoding, RNA, 9, 384, 10.1261/rna.2184703 · DOI
  42. Zaher, 2009, Fidelity at the molecular level: lessons from protein synthesis, Cell, 136, 746, 10.1016/j.cell.2009.01.036 · DOI
  43. Zaher, 2010, Hyperaccurate and error-prone ribosomes exploit distinct mechanisms during tRNA selection, Mol. Cell, 39, 110, 10.1016/j.molcel.2010.06.009 · DOI

Metadata

Authors
Savir, Y., & Tlusty, T.
Affiliations
  • Harvard University (US)
  • Institute for Advanced Study (US)
Corresponding author
Tlusty, Tsvi
Venue
Cell
Publisher
Elsevier BV
Published
2013-04
Volume
153
Issue
2
Pages
471-479
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2018622616
Cited by
57
References
2
Citations by year
2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 9 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 1
FWCI
1.88
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
ribosome, tRNA decoding, codon-anticodon pairing, energy landscape, molecular recognition, conformational change, prokaryotic ribosomes, protein synthesis
MeSH terms
Energy Metabolism, Prokaryotic Cells, Ribosomes, RNA, Transfer, Thermodynamics, Protein Biosynthesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review