Redox sensitivity of PDI. (A) In a reducing environment, PDI assumes a compact structure characterized by a 15-Å distance between the a and a′ domains. (B) In an oxidizing environment, the distance between the a and a′ domain increases to 30 Å. The increase in distance results from loss of interactions between the b′ and a′ domains that allows movement of the x-linker and a′ domains. Adapted from Wang et al.²³  (C) In a reducing environment, the disulfide bond between C397 and C400 is broken, enabling the rotation of W396. This rotation positions W396 so that it can interact with R300. The interaction between W396 and R300 brings the a′ domain in closer proximity to the b′ domain, facilitating additional interactions that lead to a more compact structure. Adapted from Wang et al.²³