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Nat Struct Mol Biol. 2014 Sep;21(9):787-93. doi: 10.1038/nsmb.2871. Epub 2014 Aug 17.

A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation on the ribosome.

Author information

1
1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
2
1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA. [3] Department of Chemistry, Yale University, New Haven, Connecticut, USA.
3
1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2].

Abstract

During peptide-bond formation on the ribosome, the α-amine of an aminoacyl-tRNA attacks the ester carbonyl carbon of a peptidyl-tRNA to yield a peptide lengthened by one amino acid. Although the ribosome's contribution to catalysis is predominantly entropic, the lack of high-resolution structural data for the complete active site in complex with full-length ligands has made it difficult to assess how the ribosome might influence the pathway of the reaction. Here, we present crystal structures of preattack and postcatalysis complexes of the Thermus thermophilus 70S ribosome at ~2.6-Å resolution. These structures reveal a network of hydrogen bonds along which proton transfer could take place to ensure the concerted, rate-limiting formation of a tetrahedral intermediate. We propose that, unlike earlier models, the ribosome and the A-site tRNA facilitate the deprotonation of the nucleophile through the activation of a water molecule.

PMID:
25132179
PMCID:
PMC4156881
DOI:
10.1038/nsmb.2871
[Indexed for MEDLINE]
Free PMC Article

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