Quality over quantity: optimizing co-translational protein folding with non-‘optimal’ synonymous codons

Abstract

Protein folding occurs on a time scale similar to peptide bond formation by the ribosome, which has long sparked speculation that altering translation rate could alter the folding mechanism or even the final folded structure of a protein in vivo. Recent results have provided strong support for this model: synonymous substitutions to codons with different usage frequency, which are often translated at different rates, have been shown to significantly alter the co-translational folding mechanism of some proteins, leading to altered cell function. Here we review recent progress towards understanding the connections between synonymous codon usage, translation rate and co-translational protein folding mechanisms.