ERp57 is essential for efficient folding of glycoproteins sharing common structural domains
ERp57 is essential for efficient folding of glycoproteins sharing common structural domains
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DOI：
10.1038/sj.emboj.7601505
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发表时间：
2007-01-10
期刊：
影响因子：
11.4
通讯作者：
Bulleid, Neil J.
中科院分区：
文献类型：
--
作者：
Jessop, Catherine E.;Chakravarthi, Seema;Bulleid, Neil J.
ERp57 是氧化还原酶蛋白质二硫键异构酶家族的成员，参与哺乳动物细胞内质网中天然二硫键的形成。该酶已被证明与钙连接蛋白和钙网蛋白相关，因此被认为是一种糖蛋白特异性氧化还原酶。在这里，我们通过捕获酶和底物之间的混合二硫化物中间体来鉴定 ERp57 的内源底物。我们的结果表明，这种酶的底物主要是高度糖基化的二硫键蛋白质。此外，我们发现底物蛋白具有共同的结构域，这表明底物特异性可能涉及特定的结构特征以及寡糖侧链的存在。我们还表明，ERp57 敲除细胞中 ERp57 的两种内源性底物的折叠受到损害，并且防止与钙联蛋白或钙网蛋白相互作用会扰乱一些（但不是全部）具有多个二硫键的底物的折叠。这些结果表明 ERp57 在特定糖蛋白底物中非天然二硫键异构化中的特定作用。
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.