Molecular mechanism of stop codon recognition by eRF1: a wobble hypothesis for peptide anticodons.
We propose that the amino acid residues 57/58 and 60/61 of eukaryotic release factors (eRF1s) (counted from the N-terminal Met of human eRF1) are responsible for stop codon recognition in protein synthesis. The proposal is based 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 second and the residues 60/61 with the third position of a stop codon. The fact that conventional eRF1s recognize all three stop codons but not the codon for tryptophan is attributed to the flexibility of the helix containing these residues. We suggest that the helix is able to assume a partly relaxed or tight conformation depending on the stop codon recognized. The restricted codon recognition observed in organisms with unconventional eRF1s is attributed mainly to the loss of flexibility of the helix due to exchanged amino acids.
Muramatsu
T
T
Biophysics Division, National Cancer Research Institute, Tokyo, Japan. tmuramat@ncc.go.jp
Heckmann
K
K
Kitanaka
C
C
Kuchino
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000926:Anticodon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018388:Codon, Terminator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism; D019143:Evolution, Molecular; D005815:Genetic Code / Q000235:genetics / Q000502:physiology; D006801:Humans; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010454:Peptide Termination Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013379:Substrate Specificity; D016808:Tetrahymena thermophila / Q000235:genetics / Q000378:metabolism
D000926:Anticodon; D018388:Codon, Terminator; C489002:ETF1 protein, human; D010454:Peptide Termination Factors