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Replacement of domain b of human protein disulfide isomerase‐related protein with domain b ′ of human protein disulfide isomerase dramatically increases its chaperone activity
Author(s) -
Horibe Tomohisa,
Iguchi Daisuke,
Masuoka Toshio,
Gomi Mitsuhiro,
Kimura Taiji,
Kikuchi Masakazu
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.03.103
Subject(s) - protein disulfide isomerase , chaperone (clinical) , chemistry , isomerase , biochemistry , mutant , disulfide bond , enzyme , gene , medicine , pathology
We have reported that human protein disulfide isomerase‐related protein (hPDIR) has isomerase and chaperone activities that are lower than those of the human protein disulfide isomerase (hPDI), and that the b domain of hPDIR is critical for its chaperone activity [J. Biol. Chem. 279 (2004) 4604]. To investigate the basis of the differences between hPDI and hPDIR, and to determine the functions of each hPDIR domain in detail, we constructed several hPDIR domain mutants. Interestingly, when the b domain of hPDIR was replaced with the b ′ domain of hPDI, a dramatic increase in chaperone activity that was close to that of hPDI itself was observed. However, this mutant showed decreased oxidative refolding of α1‐antitrypsin. The replacement of the b domain of hPDIR with the c domain of hPDI also increased its chaperone activity. These observations suggest that putative peptide‐binding sites of hPDI determine both its chaperone activity and its substrate specificity.