Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation

To investigate the possible influence of the local rates of translation on protein folding, 16 consecutive rare (in Escherichia coli) codons in the chloramphenicol acetyltransferase (CAT) gene have been replaced by frequent ones. Site-directed silent mutagenesis reduced the pauses in translation of...

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Bibliographic Details
Published in:FEBS letters 1999-12, Vol.462 (3), p.387-391
Main Authors: Komar, Anton A, Lesnik, Thierry, Reiss, Claude
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Chloramphenicol acetyltransferase
Chloramphenicol O-Acetyltransferase - genetics
Chloramphenicol O-Acetyltransferase - metabolism
Codon
Codon usage
Cotranslational folding
Escherichia coli - metabolism
Misfolding
Molecular Sequence Data
Mutagenesis
Plasmids - metabolism
Protein Biosynthesis
Protein Folding
Ribosomes - metabolism
Time Factors
Translation
Translational pause
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Summary:To investigate the possible influence of the local rates of translation on protein folding, 16 consecutive rare (in Escherichia coli) codons in the chloramphenicol acetyltransferase (CAT) gene have been replaced by frequent ones. Site-directed silent mutagenesis reduced the pauses in translation of CAT in E. coli S30 extract cell-free system and led to the acceleration of the overall rate of CAT protein synthesis. At the same time, the silently mutated protein (with unaltered protein sequence) synthesized in the E. coli S30 extract system was shown to possess 20% lower specific activity. The data suggest that kinetics of protein translation can affect the in vivo protein-folding pathway, leading to increased levels of protein misfolding.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(99)01566-5