Specificity in substrate binding by protein folding catalysts: tyrosine and tryptophan residues are the recognition motifs for the binding of peptides to the pancreas-specific protein disulfide isomerase PDIp.
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.
Ruddock
L W
LW
Department of Biosciences, University of Kent, Canterbury, United Kingdom.
Freedman
R B
RB
Klappa
P
P
D000595:Amino Acid Sequence; D002384:Catalysis; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology*; D010455:Peptides / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D013379:Substrate Specificity; D014364:Tryptophan / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D010455:Peptides; D014443:Tyrosine; D014364:Tryptophan; D019704:Protein Disulfide-Isomerases