Winter, J. and Klappa, P. and Freedman, R.B. and Lilie, H. and Rudolph, R. (2002) Catalytic activity and chaperone function of human protein-disulfide isomerase are required for the efficient refolding of proinsulin. Journal of Biological Chemistry, 277 (1). pp. 310-317. ISSN 0021-9258.
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Protein-disulfide isomerase (PDI) catalyzes the formation, rearrangement, and breakage of disulfide bonds and is capable of binding peptides and unfolded proteins in a chaperone-like manner. In this study we examined which of these functions are required to facilitate efficient refolding of denatured and reduced proinsulin. In our model system, PDI and also a PDI mutant having only one active site increased the rate of oxidative folding when present in catalytic amounts. PDI variants that are completely devoid of isomerase activity are not able to accelerate proinsulin folding, but can increase the yield of refolding, indicating that they act as a chaperone. Maximum refolding yields, however, are only achieved with wild-type PDI. Using genistein, an inhibitor for the peptide-binding site, the ability of PDI to prevent aggregation of folding proinsulin was significantly suppressed. The present results suggest that PDI is acting both as an isomerase and as a chaperone during folding and disulfide bond formation of proinsulin.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Protein Science Group|
|Depositing User:||Sue Davies|
|Date Deposited:||19 Dec 2007 17:49|
|Last Modified:||05 Sep 2011 23:19|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/46 (The current URI for this page, for reference purposes)|
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