A pancreas-specific glycosylated protein disulphide-isomerase binds to misfolded proteins and peptides with an interaction inhibited by oestrogens.
Using a cross-linking approach, we have demonstrated that radiolabeled model peptides or misfolded proteins specifically interact in vitro with two different luminal proteins in a crude extract from sheep pancreas microsomes. One of the proteins was identified as protein disulphide-isomerase (PDI), the other one was a related protein (PDIp). We have shown that PDIp was expressed exclusively in the pancreas. Interspecies conservation of PDIp was confirmed and, unlike other members of the PDI family, PDIp from various sources was found to be a glycoprotein. PDIp interacted with peptides and also a misfolded protein, but not with native proteins, suggesting that it might act as a molecular chaperone. The initial binding process was independent of the presence of Cys residues in the probed peptides. Certain oestrogens strongly inhibited the interaction between peptides and PDIp, with 17beta-oestradiol being the most potent inhibitor.
Klappa
P
P
Research School of Biosciences, University of Kent, Canterbury, UK.
Stromer
T
T
Zimmermann
R
R
Ruddock
L W
LW
Freedman
R B
RB
D000818:Animals; D002417:Cattle; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D006023:Glycoproteins / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000201:enzymology; D018832:Molecular Chaperones / Q000502:physiology; D010179:Pancreas / Q000201:enzymology*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides; D011485:Protein Binding / Q000502:physiology; D019704:Protein Disulfide-Isomerases / Q000737:chemistry*; D017510:Protein Folding; D051381:Rats; D012260:Ribonucleases / Q000737:chemistry; D012756:Sheep; D013004:Somatostatin / Q000378:metabolism; D014862:Wasp Venoms / Q000378:metabolism
D004791:Enzyme Inhibitors; D004967:Estrogens; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D010455:Peptides; D014862:Wasp Venoms; D004958:Estradiol; D013004:Somatostatin; C037500:mastoparan; D012260:Ribonucleases; D019704:Protein Disulfide-Isomerases