Protien disulfide isomerase is a multidomain protein operating as an essential folding catalyst. The b' and a' domains of this enzyme exhibit a domain rearrangement depending on the redox states of the a' domain, which is coupled with an open-closed conformational change of substrate-binding hydrophobic surface. Here we performed crystallographic analysis along with molecular dynamics simulations to study the structural mechanisms underlying this domain rearrangement. Based on our data, we propose that oxidization of the a' active site induces conformational changes in its b'-interacting segments, which is concealed by crystal packing, resulting in segregation of these two domains. (C) 2014 Elsevier B.V. All rights reserved.