Jessop, C.E., Chakravarthi, S., Garbi, N., Hämmerling, G.J., Lovell, S. and Bulleid, N.J. (2007) ERp57 is essential for efficient folding of glycoproteins sharing common structural domains. EMBO Journal, 26(1), pp. 28-40. (doi: 10.1038/sj.emboj.7601505)
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Abstract
ERp57 is a member of the protein disulphide isomerase family of oxidoreductases, which are involved in native disulphide bond formation in the endoplasmic reticulum of mammalian cells. This enzyme has been shown to be associated with both calnexin and calreticulin and, therefore, has been proposed to be a glycoprotein-specific oxidoreductase. Here, we identify endogenous substrates for ERp57 by trapping mixed disulphide intermediates between enzyme and substrate. Our results demonstrate that the substrates for this enzyme are mostly heavily glycosylated, disulphide bonded proteins. In addition, we show that the substrate proteins share common structural domains, indicating that substrate specificity may involve specific structural features as well as the presence of an oligosaccharide side chain. We also show that the folding of two of the endogenous substrates for ERp57 is impaired in ERp57 knockout cells and that prevention of an interaction with calnexin or calreticulin perturbs the folding of some, but not all, substrates with multiple disulphide bonds. These results suggest a specific role for ERp57 in the isomerisation of non-native disulphide bonds in specific glycoprotein substrates.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Bulleid, Professor Neil |
Authors: | Jessop, C.E., Chakravarthi, S., Garbi, N., Hämmerling, G.J., Lovell, S., and Bulleid, N.J. |
Subjects: | Q Science > QH Natural history > QH345 Biochemistry |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | EMBO Journal |
ISSN: | 0261-4189 |
ISSN (Online): | 1460-2075 |
Published Online: | 14 December 2006 |
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