The structure in solution of the b domain of protein disulfide isomerase

Protein disulfide isomerase (PDI) is a multifunctional protein of the endop lasmic reticulum, which catalyzes the formation, breakage and rearrangement of disulfide bonds during protein folding. It consists of four domains des ignated a, b, b' and a'. Both a and a' domains contain an active site with the sequence motif -Cys-Gly-His-Cys-involved directly in thiol-disulfide ex change reactions. As expected these domains have structures very similar to the ubiquitous redox protein thioredoxin. A low-resolution NMR structure o f the b domain revealed that this domain adopts a fold similar to the PDI a domain and thioredoxin [Kemmink, J., Darby, N.J., Dijkstra, K., Nilges, M. and Creighton, T.E. (1997) Gun: Biol., 7, 239-245]. A refined ensemble of solution structures based on the input of 1865 structural restraints shows that the structure of PDI b is well defined throughout the complete protein except for about 10 residues at the C-terminus of the sequence. N-15 relax ation data show that these residues are disordered and not part of this str uctural domain. Therefore the domain boundaries of PDI can now be fixed wit h reasonable precision. Structural comparison of the PDI b domain with thio redoxin and PDI a reveals several features important for thiol-disulfide ex change activity.