ERp57 is essential for efficient folding of glycoproteins sharing common structural domains

被引:166
作者
Jessop, Catherine E.
Chakravarthi, Seema
Garbi, Natalio
Haemmerling, Guenter J.
Lovell, Simon
Bulleid, Neil J.
机构
[1] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
[2] German Canc Res Ctr, DKFZ, D-6900 Heidelberg, Germany
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
clusterin; disulphide bonds; ERp57; integrin; protein disulphide isomerase;
D O I
10.1038/sj.emboj.7601505
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:28 / 40
页数:13
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