期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：4
页码：1819-1824
DOI：10.1073/pnas.032457599
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The mechanism of stop codon recognition during translation has long been a puzzle. Only recently has it been established that a tripeptide in the bacterial release factors (RFs) 1 and 2 serves as the "anticodon" in deciphering stop codons in mRNA. However, the molecular basis of the accuracy of stop codon recognition is unknown. Although specific tripeptides in the RFs are primarily responsible for selective reading of cognate stop codons, charge-flip variant RF proteins, altered at conserved Glu residues adjacent to the tripeptide-anticodon, are shown here to be crucial to codon recognition. Changes of these Glu residues are capable of triggering polypeptide release at noncognate stop codons and also at sense codons. These changes also reverse the growth inhibition by RFs containing "harmful" tripeptide-anticodon changes. These findings suggest that electrostatic interactions involving negative charges in domain C of the RFs mediate their accurate docking in the ribosome. Our results also establish that the charge flipping creates a phenotype/translation termination by "codon bypassing" via relaxed positioning of the RF tripeptide-anticodon in the decoding pocket of the ribosome.
