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

FEBS Letters

Lesnik, Thierry¹  Komar, Anton A¹  Reiss, Claude¹ 

[1] Centre de Génétique Moléculaire, CNRS, F-91198 Gif-sur-Yvette cedex, France

关键词: Chloramphenicol acetyltransferase;    Codon usage;    Translation;    Translational pause;    Cotranslational folding;    Misfolding;   

DOI  :  10.1016/S0014-5793(99)01566-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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folding, 16 consecutive rare (in Escherichia coli) codons in the chloramphenicol acetyltransferase (CAT) gene have been replaced by frequent ones.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.

【 授权许可】

Unknown