A PANCREAS-SPECIFIC GLYCOSYLATED PROTEIN DISULFIDE-ISOMERASE BINDS TOMISFOLDED PROTEINS AND PEPTIDES WITH AN INTERACTION INHIBITED BY ESTROGENS

Using a cross-linking approach, we have demonstrated that radiolabeled model peptides or misfolded proteins specifically interact in vitro w ith two different luminal proteins in a crude extract from sheep pancr eas microsomes. One of the proteins was identified as protein disulphi de-isomerase (PDI), the other one was a related protein (PDIp). We hav e shown that PDIp was expressed exclusively in the pancreas. Interspec ies conservation of PDIp, was confirmed and, unlike other members of t he PDI family, PDIp from various sources was found to be a glycoprotei n. PDIp interacted with peptides and also a misfolded protein, but not with native proteins, suggesting that it might act as a molecular cha perone. The inital binding process was independent of the presence of Cys residues in the probed peptides. Certain oestrogens strongly inhib ited the interaction between peptides and PDIp, with 17 beta-oestradio l being the most patent inhibitor.