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Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation
Author(s) -
Komar Anton A,
Lesnik Thierry,
Reiss Claude
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01566-5
Subject(s) - protein biosynthesis , translation (biology) , chloramphenicol acetyltransferase , eukaryotic translation , ribosome , mutagenesis , protein folding , shine dalgarno sequence , eif4ebp1 , escherichia coli , biology , start codon , gene , folding (dsp implementation) , stop codon , chemistry , microbiology and biotechnology , biochemistry , messenger rna , mutation , gene expression , rna , reporter gene , electrical engineering , engineering
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folding, 16 consecutive rare (in Escherichia coli ) codons in the chloramphenicol acetyltransferase (CAT) gene have been replaced by frequent ones.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.