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Peptide release on the ribosome is catalyzed by protein release factors (RFs) on recognition of stop codons positioned in the A site of the small ribosomal subunit. Here we show that the 2′ OH of the peptidyl–tRNA substrate plays an essential role in catalysis of the peptide release reaction. These observations parallel earlier studies of the mechanism of the peptidyl transfer reaction and argue that related mechanisms are at the heart of catalysis for these reactions.

Peptide release on the ribosome depends critically on the 2′ OH of the peptidyl–tRNA substrate