The Thiol-dependent Reductase ERp57 Interacts Specifically with N-Glycosylated Integral Membrane Proteins*
- From the School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom
Abstract
The lumen of the endoplasmic reticulum contains a number of distinct molecular chaperones and folding factors, which modulate the folding and assembly of newly synthesized proteins and protein complexes. A subset of these luminal components are specific for glycoproteins, and, like calnexin and calreticulin, the thiol-dependent reductase ERp57 has been shown to interact specifically with soluble secretory proteins bearingN-linked carbohydrate.
Calnexin and calreticulin also interact with glycosylated integral membrane proteins, and in this study we have examined the interaction of ERp57 with these substrates. As with soluble proteins, the binding of ERp57 to an integral membrane protein is dependent upon the protein bearing an N-glycan that has undergone glucose trimming. Furthermore, ERp57 binds to newly synthesized glycoproteins in combination with either calnexin or calreticulin. We propose that ERp57 acts in concert with calnexin and calreticulin to modulate glycoprotein folding and enforce the glycoprotein specific quality control mechanism operating in the endoplasmic reticulum.
Footnotes
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↵* This work was supported by grants from the Biotechnology and Biological Sciences Research Council.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Biotechnology and Biological Sciences Research Council Advanced Research Fellow. To whom correspondence should be addressed. Tel.: 44-161-275-5070; Fax: 44-161-275-5082.
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↵1 The abbreviations used are: ER, endoplasmic reticulum; BMH, bismaleimidohexane; CST, castanospermine; dMM, 1-deoxymannojirimycin; ERp57, endoplasmic reticulum protein of 57 kDa; Glut 1, glucose transporter; GlyC, glycophorin C; GT155, 155-amino acid truncation of Glut 1 glucose transporter; PDI, protein-disulfide isomerase; PMSF, phenylmethylsulfonyl fluoride; SMCC, succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate.
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- Received January 13, 1997.
- Revision received March 17, 1997.
