Fig. 6.

For misfolding-prone proteins that can fold cotranslationally, the overall folding rate is optimized if the nascent chain has time to start folding at the earliest length at which stable folding can occur. At this point, the chain’s folding landscape is still relatively smooth (blue arrow). In the case that the nascent chain’s folding rate at this critical length is slightly slower than the synthesis rate, then slowing down synthesis using rare codons roughly 30 amino acids downstream is beneficial. In contrast, delaying folding until further synthesis is complete (red arrow) leads to deep kinetic traps stabilized by C-terminal residues, which significantly slow folding.