Ribosome slowed by mutation to streptomycin resistance

ALTHOUGH the basic mechanisms of protein synthesis are now rather well understood, particularly in Escherichia coli , it is less clear how the high accuracy of this process is achieved. (The error rate in protein synthesis in E. coli seems to be about one in 10 4 amino acid misincorporations (Edelma...

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Bibliographic Details
Published in:Nature (London) 1976-08, Vol.262 (5569), p.617-619
Main Authors: GALAS, DAVID J, BRANSCOMB, ELBERT W
Format: Article
Language:English
Subjects:
Drug Resistance, Microbial
Escherichia coli
Galactosidases - biosynthesis
Humanities and Social Sciences
Kinetics
letter
multidisciplinary
Mutation
Peptide Chain Elongation, Translational
Ribosomes - metabolism
Science
Science (multidisciplinary)
Streptomycin
Transcription, Genetic
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Summary:ALTHOUGH the basic mechanisms of protein synthesis are now rather well understood, particularly in Escherichia coli , it is less clear how the high accuracy of this process is achieved. (The error rate in protein synthesis in E. coli seems to be about one in 10 4 amino acid misincorporations (Edelman and Gallant, unpublished results, and our own unpublished data)). A major site determining accuracy in protein synthesis is the ribosome, and in addition to the ribosome-mediated effects on accuracy ( in vivo and in vitro ) of various metal ions, aminoglycoside antibiotics and organic solvents, there are ribosomal mutations which increase or decrease accuracy 2 . Certain mutations of the 30S ribosomal protein SI2 conferring streptomycin resistance (the strA locus) enhance accuracy 3–5 , whereas certain mutations in the S4 protein (the ram locus) are known to decrease accuracy 6 . The strA mutations are restrictive (reducing) in their effect on both missense and nonsense suppression in vivo and on miscoding in vitro 3 , the ram mutation, on the other hand, has the opposite effect in both cases 6 . It is possible that it is the kinetics of polypeptide synthesis at the ribosome that determines accuracy and that the kinetics in turn are affected by the strA and ram mutations. Because the same transfer RNA (tRNA) discrimination kinetics that may determine accuracy may also contribute to the elongation speed, we have investigated the effect of mutation to streptomycin resistance on the speed of polypeptide elongation.
ISSN:0028-0836
1476-4687
DOI:10.1038/262617b0