Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins

Jessop, C.E., Watkins, R.H., Simmons, J.J., Tasab, M. and Bulleid, N.J. (2009) Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins. Journal of Cell Science, 122(23), pp. 4287-4295. (doi:10.1242/jcs.059154)

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Abstract

At least 17 members of the protein disulphide isomerase (PDI) family of oxidoreductases are present in the endoplasmic reticulum (ER) of mammalian cells. They are thought to catalyse disulphide formation to aid folding or to regulate protein function; however, little is known about their individual functions. Here, we show that some proteins that enter the ER are clients for single oxidoreductases, whereas others are clients for several PDI-like enzymes. We previously identified potential substrates for ERp57, and here identify substrates for ERp18 and ERp46. In addition, we analysed the specificity of substrates towards PDI, ERp72, ERp57, ERp46, ERp18 and P5. Strikingly, ERp18 shows specificity towards a component of the complement cascade, pentraxin-related protein PTX3, whereas ERp46 has specificity towards peroxiredoxin-4, a thioredoxin peroxidase. By contrast, most PDI family members react with Ero1{alpha}. Moreover, P5 forms a non-covalent complex with immunoglobulin heavy chain binding protein (BiP) and shows specificity towards BiP client proteins. These findings highlight cooperation between BiP and P5, and demonstrate that individual PDI family members recognise specific substrate proteins.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bulleid, Professor Neil
Authors: Jessop, C.E., Watkins, R.H., Simmons, J.J., Tasab, M., and Bulleid, N.J.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Cell Science
Publisher:The Company of Biologists Ltd.
ISSN:0021-9533
ISSN (Online):1477-9137
Published Online:03 November 2009
Copyright Holders:Copyright © 2009 Company of Biologists
First Published:First published in Journal of Cell Science122(23): 4287-4295
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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