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

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 pre-attack and post-catalysis 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. Unlike earlier models, we propose that the ribosome and the A-site tRNA facilitate the deprotonation of the nucleophile through the activation of a water molecule.