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

FEBS Lett. 1999 Dec 3;462(3):387-91. doi: 10.1016/s0014-5793(99)01566-5.


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folding, 16 consecutive rare (in Escherichia coli) codons in the chloramphenicol acetyltransferase (CAT) gene have been replaced by frequent ones.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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Codon*
  • Escherichia coli / metabolism
  • Molecular Sequence Data
  • Mutagenesis*
  • Plasmids / metabolism
  • Protein Biosynthesis*
  • Protein Folding*
  • Ribosomes / metabolism*
  • Time Factors


  • Codon
  • Chloramphenicol O-Acetyltransferase