Klappa, Peter and Koivunen, Peppi and Pirneskoski, Annamari and Karvonen, P. and Ruddock, Lloyd W. and Kivirikkos, Kari I. and 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)
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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.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences|
|Depositing User:||O.O. Odanye|
|Date Deposited:||02 Apr 2009 17:25|
|Last Modified:||16 Jul 2014 11:39|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/16288 (The current URI for this page, for reference purposes)|