Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain
Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain
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DOI：
10.1074/jbc.m207831200
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发表时间：
2002-11-22
影响因子：
4.8
通讯作者：
Cresswell, P
中科院分区：
文献类型：
--
作者：
Kang, SJ;Cresswell, P
膜糖蛋白 CD1 家族的成员可以向 T 淋巴细胞呈递抗原脂质。与主要组织相容性复合物 I 类分子一样，它们在内质网 (ER) 中形成重链和 β(2)-微球蛋白 (β(2)m) 的异二聚体复合物。然而，脂质抗原的结合发生在内体区室中，类似于 II 类分子，并且发生在质膜上。与主要组织相容性复合物 I 类或 CD1b 分子需要 β(2)m 才能退出 ER 不同，CD1d 可以在细胞表面表达为游离重链或与 β(2)m 相关。这些差异促使我们研究 CD1d 生物合成和成熟的早期事件以及 ER 伴侣在其组装中的作用。在这里，我们表明 CD1d 在 ER 中与钙连接蛋白和钙网蛋白以及硫醇氧化还原酶 ERp57 结合，其方式依赖于其 N 连接聚糖的葡萄糖修剪。如果分子伴侣相互作用被葡萄糖苷酶抑制剂栗精胺或 N-丁基脱氧野尻霉素阻断，则 CD1d 重链中完整的二硫键形成会受到严重损害。 CD1d 重链中至少一个二硫键的形成与其与 ERp57、钙联蛋白和钙网蛋白的葡萄糖修饰依赖性关联偶联。
Members of the CD1 family of membrane glycoproteins can present antigenic lipids to T lymphocytes. Like major histocompatibility complex class I molecules, they form a heterodimeric complex of a heavy chain and beta(2)-microglobulin (beta(2)m) in the endoplasmic reticulum (ER). Binding of lipid antigens, however, takes place in endosomal compartments, similar to class II molecules, and on the plasma membrane. Unlike major histocompatibility complex class I or CD1b molecules, which need beta(2)m to exit the ER, CD1d can be expressed on the cell surface as either a free heavy chain or associated with beta(2)m. These differences led us to investigate early events of CD1d biosynthesis and maturation and the role of ER chaperones in its assembly. Here we show that CD1d associates in the ER with both calnexin and calreticulin and with the thiol oxidoreductase ERp57 in a manner dependent on glucose trimming of its N-linked glycans. Complete disulfide bond formation in the CD1d heavy chain was substantially impaired if the chaperone interactions were blocked by the glucosidase inhibitors castanospermine or N-butyldeoxynojirimycin. The formation of at least one of the disulfide bonds in the CD1d heavy chain is coupled to its glucose trimming-dependent association with ERp57, calnexin, and calreticulin.