BPTI folding revisited: switching a disulfide into methylene thioacetal reveals a previously hidden path.

ABSTRACT: Bovine pancreatic trypsin inhibitor (BPTI) is a 58-residue protein that is stabilized by three disulfide bonds at positions 5-55, 14-38 and 30-51. Widely studied for about 50 years, BPTI represents a folding model for many disulfide-rich proteins. In the study described below, we replaced the solvent exposed 14-38 disulfide bond with a methylene thioacetal bridge in an attempt to arrest the folding pathway of the protein at its two well-known intermediates, N' and N*. The modified protein was expected to be unable to undergo the rate-determining step in the widely accepted BPTI folding mechanism: the opening of the 14-38 disulfide bond followed by rearrangements that leads to the native state, N. Surprisingly, instead of halting BPTI folding at N' and N*, we uncovered a hidden pathway invo

SUBMITTER: Mousa R 

PROVIDER: S-EPMC5982216 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature