Cotranslational folding allows misfolding-prone proteins to circumvent deep kinetic traps.

ABSTRACT: Many large proteins suffer from slow or inefficient folding in vitro. It has long been known that this problem can be alleviated in vivo if proteins start folding cotranslationally. However, the molecular mechanisms underlying this improvement have not been well established. To address this question, we use an all-atom simulation-based algorithm to compute the folding properties of various large protein domains as a function of nascent chain length. We find that for certain proteins, there exists a narrow window of lengths that confers both thermodynamic stability and fast folding kinetics. Beyond these lengths, folding is drastically slowed by nonnative interactions involving C-terminal residues. Thus, cotranslational folding is predicted to be beneficial because it allows proteins to tak

SUBMITTER: Bitran A 

PROVIDER: S-EPMC6983386 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature