Structural basis of redox-dependent substrate binding of protein disulfide isomerase.

ABSTRACT: Protein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b' and a' domains provide substrate binding sites and undergo an open-closed domain rearrangement depending on the redox states of the a' domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37-Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b'-a' domains in complex with an undecapeptide corresponding to this segment. The

SUBMITTER: Yagi-Utsumi M 

PROVIDER: S-EPMC4563560 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature