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Mutations that destabilize the a ' domain of human protein-disulfide isomerase indirectly affect peptide binding

Klappa, Peter, Koivunen, Peppi, Pirneskoski, Annamari, Karvonen, P., Ruddock, Lloyd W., Kivirikkos, Kari I., Freedman, Robert B. (2000) Mutations that destabilize the a ' domain of human protein-disulfide isomerase indirectly affect peptide binding. Journal of Biological Chemistry, 275 (18). pp. 13213-13218. ISSN 0021-9258. (doi:10.1074/jbc.275.18.13213) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:16288)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1074/jbc.275.18.13213

Abstract

Protein-disulfide isomerase (PDI) is a catalyst of folding of disulfide-bonded proteins and also a multifunctional polypeptide that acts as the beta-subunit in the prolyl 4-hydroxylase alpha(2)beta(2)-tetramer (P4H) and the microsomal triglyceride transfer protein alpha beta-dimer. The principal peptide-binding site of PDI is located in the b' domain, but all domains contribute to the binding of misfolded proteins, Mutations in the C-terminal part of the a' domain have significant effects on the assembly of the P4H tetramer and other functions of PDI, In this study we have addressed the question of whether these mutations in the C-terminal part of the a' domain, which affect P4H assembly, also affect peptide binding to PDI. We observed a strong correlation between P4H assembly competence and peptide binding; mutants of PDI that failed to form a functional P4H tetramer were also inactive in peptide binding. However, there was also a correlation between inactivity in these assays and indicators of conformational disruption, such as protease sensitivity. Peptide binding activity could be restored in inactive, protease-sensitive mutants by selective proteolytic removal of the mutated a' domain. Hence we propose that structural changes in the a' domain indirectly affect peptide binding to the b' domain.

Item Type: Article
DOI/Identification number: 10.1074/jbc.275.18.13213
Subjects: Q Science
R Medicine
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: O.O. Odanye
Date Deposited: 02 Apr 2009 17:25 UTC
Last Modified: 16 Nov 2021 09:54 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/16288 (The current URI for this page, for reference purposes)

University of Kent Author Information

Klappa, Peter.

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Ruddock, Lloyd W..

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Freedman, Robert B..

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