Reduction of protein disulfide isomerase results in open conformations and stimulates dynamic exchange between structural ensembles.

ABSTRACT: Human protein disulfide isomerase (PDI) is an essential redox-regulated enzyme required for oxidative protein folding. It comprises four thioredoxin domains, two catalytically active (a, a') and two inactive (b, b'), organized to form a flexible abb'a' U-shape. Snapshots of unbound oxidized and reduced PDI have been obtained by X-ray crystallography. Yet, how PDI's structure changes in response to the redox environment and inhibitor binding remains controversial. Here, we used multiparameter confocal single-molecule FRET to track the movements of the two catalytic domains with high temporal resolution. We found that at equilibrium, PDI visits three structurally distinct conformational ensembles, two "open" (O₁ and O₂) and one "closed" (C). We show that the redox envir

SUBMITTER: Chinnaraj M 

PROVIDER: S-EPMC9352907 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature