Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release.
Peptide release on the ribosome is catalyzed in the large subunit peptidyl transferase center by release factors on recognition of stop codons in the small subunit decoding center. Here we examine the role of the decoding center in this process. Mutation of decoding center nucleotides or removal of 2'OH groups from the codon--deleterious in the related process of tRNA selection--has only mild effects on peptide release. The miscoding antibiotic paromomycin, which binds the decoding center and promotes the critical steps of tRNA selection, instead dramatically inhibits peptide release. Differences in the kinetic mechanism of paromomycin inhibition on stop and sense codons, paired with correlated structural changes monitored by chemical footprinting, suggest that recognition of stop codons by release factors induces specific structural rearrangements in the small subunit decoding center. We propose that, like other steps in translation, the specificity of peptide release is achieved through an induced-fit mechanism.
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Elaine M
EM
Youngman
Shan L
SL
He
Laura J
LJ
Nikstad
Rachel
R
Green
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018388:Codon, Terminator / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010303:Paromomycin / Q000494:pharmacology; D010454:Peptide Termination Factors / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012270:Ribosomes / Q000737:chemistry* / Q000187:drug effects; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D018388:Codon, Terminator; D003854:Deoxyribonucleotides; D010454:Peptide Termination Factors; D010455:Peptides; D010303:Paromomycin