Quality control by the ribosome following peptide bond formation.
The overall fidelity of protein synthesis has been thought to rely on the combined accuracy of two basic processes: the aminoacylation of transfer RNAs with their cognate amino acid by the aminoacyl-tRNA synthetases, and the selection of cognate aminoacyl-tRNAs by the ribosome in cooperation with the GTPase elongation factor EF-Tu. These two processes, which together ensure the specific acceptance of a correctly charged cognate tRNA into the aminoacyl (A) site, operate before peptide bond formation. Here we report the identification of an additional mechanism that contributes to high fidelity protein synthesis after peptidyl transfer, using a well-defined in vitro bacterial translation system. In this retrospective quality control step, the incorporation of an amino acid from a non-cognate tRNA into the growing polypeptide chain leads to a general loss of specificity in the A site of the ribosome, and thus to a propagation of errors that results in abortive termination of protein synthesis.
Zaher
Hani S
HS
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Green
Rachel
R
D049148:Aminoacylation; D000926:Anticodon / Q000235:genetics; D020137:Base Pair Mismatch / Q000235:genetics; D055162:Biocatalysis; D003062:Codon / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D010443:Peptide Chain Termination, Translational; D010454:Peptide Termination Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D000926:Anticodon; D003062:Codon; D029968:Escherichia coli Proteins; D010454:Peptide Termination Factors; C489006:prfB protein, E coli; C489007:prfC protein, E coli; D012343:RNA, Transfer