Synonymous codon substitutions perturb cotranslational protein folding in vivo and impair cell fitness.

ABSTRACT: In the cell, proteins are synthesized from N to C terminus and begin to fold during translation. Cotranslational folding mechanisms are therefore linked to elongation rate, which varies as a function of synonymous codon usage. However, synonymous codon substitutions can affect many distinct cellular processes, which has complicated attempts to deconvolve the extent to which synonymous codon usage can promote or frustrate proper protein folding in vivo. Although previous studies have shown that some synonymous changes can lead to different final structures, other substitutions will likely be more subtle, perturbing predominantly the protein folding pathway without radically altering the final structure. Here we show that synonymous codon substitutions encoding a single essential enzyme lead

SUBMITTER: Walsh IM 

PROVIDER: S-EPMC7035613 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature