Using a cross-linking approach, we recently demonstrated
that radiolabeled peptides or misfolded proteins specifically
interact in vitro with two luminal proteins in crude extracts
from pancreas microsomes. The proteins were the folding
catalysts protein disulfide isomerase (PDI) and PDIp, a
glycosylated, PDI-related protein, expressed exclusively
in the pancreas. In this study, we explore the specificity
of these proteins in binding peptides and related ligands
and show that tyrosine and tryptophan residues in peptides
are the recognition motifs for their binding by PDIp. This
peptide-binding specificity may reflect the selectivity
of PDIp in binding regions of unfolded polypeptide during
catalysis of protein folding.