Molecular mechanism of stop codon recognition by eRF1: a wobble hypothesisfor peptide anticodons

We propose that the amino acid residues 57/58 and 60/61 of eukaryotic relea se factors (eRF1s) (counted from the N-terminal Met of human eRF1) are resp onsible for stop codon recognition in protein synthesis, The proposal is ba sed on amino acid exchanges in these positions in the eRF1s of two ciliates that reassigned one or two stop codons to sense codons in evolution and on the crystal structure of human eRF1, The proposed mechanism of stop codon recognition assumes that the amino acid residues 57/58 interact with the se cond and the residues 60/61 with the third position of a stop codon, The fa ct that conventional eRF1s recognize all three stop codons but not the codo n for tryptophan is attributed to the flexibility of the helix containing t hese residues. We suggest that the helix is able to assume a partly relaxed or tight conformation depending on the stop codon recognized. The restrict ed codon recognition observed in organisms with unconventional eRF1s is att ributed mainly to the loss of flexibility of the helix due to exchanged ami no acids. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.