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The b′ domain provides the principal peptide‐binding site of protein disulfide isomerase but all domains contribute to binding of misfolded proteins
Author(s) -
Klappa Peter,
Ruddock Lloyd W.,
Darby Nigel J.,
Freedman Robert B.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.4.927
Subject(s) - protein disulfide isomerase , biochemistry , biology , protein folding , foldase , peptide , binding site , binding domain , isomerase , escherichia coli , enzyme , groel , gene
Protein disulfide isomerase (PDI) is a very efficient catalyst of folding of many disulfide‐bonded proteins. A great deal is known about the catalytic functions of PDI, while little is known about its substrate binding. We recently demonstrated by cross‐linking that PDI binds peptides and misfolded proteins, with high affinity but broad specificity. To characterize the substrate‐binding site of PDI, we investigated the interactions of various recombinant fragments of human PDI, expressed in Escherichia coli , with different radiolabelled model peptides. We observed that the b′ domain of human PDI is essential and sufficient for the binding of small peptides. In the case of larger peptides, specifically a 28 amino acid fragment derived from bovine pancreatic trypsin inhibitor, or misfolded proteins, the b′ domain is essential but not sufficient for efficient binding, indicating that contributions from additional domains are required. Hence we propose that the different domains of PDI all contribute to the binding site, with the b′ domain forming the essential core.

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