Calreticulin and calnexin interact with different protein and glycan determinants during the assembly of MHC class I.
Calreticulin and calnexin interact with different protein and glycan determinants during the assembly of MHC class I.
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DOI：
10.4049/jimmunol.160.11.5404
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发表时间：
1998-06
影响因子：
4.4
通讯作者：
M. Harris;Y. Y. Yu-Y.;C. Kindle;Ted H. Hansen;J. Solheim
中科院分区：
文献类型：
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作者：
M. Harris;Y. Y. Yu-Y.;C. Kindle;Ted H. Hansen;J. Solheim
在肽结合之前，多种内质网（ER）蛋白与I类相关，包括钙连接蛋白、TAP、钙网蛋白和tapasin。尽管这些ER蛋白中的任何一种的选择性功能很难定义，但它们单独或组合地执行I类的两种一般伴侣功能。它们促进I类异源三聚体分子（重（H）链、β 2m和肽）的组装，并且它们在ER中保留不完全组装的复合物。在这项研究中，我们提出的证据表明，钙网蛋白明显不同于钙连接蛋白，它如何与I类。关于协会的结构基础，在α 1结构域和α 3结构域中的位置227的氨基酸残基的寡糖部分都被发现是关键的I类与钙网蛋白的相互作用。有趣的是，钙网蛋白显示敏感性I类肽结合，即使在TAP缺陷的人类或小鼠细胞。因此，钙网蛋白在其可相互作用的I类分子的结构和构象方面明显比钙连接蛋白更具有特异性。
Before peptide binding, a variety of endoplasmic reticulum (ER) proteins are associated with class I including calnexin, TAP, calreticulin, and tapasin. Although the selective functions of any one of these ER proteins have been difficult to define, individually or in combination they perform two general chaperone functions for class I. They promote assembly of the class I heterotrimeric molecule (heavy (H) chain, beta2m, and peptide) and they retain incompletely assembled complexes in the ER. In this study, we present evidence that calreticulin clearly differs from calnexin in how it associates with class I. Regarding the structural basis of the association, the oligosaccharide moiety in the alpha1 domain and the amino acid residue at position 227 in the alpha3 domain were both found to be critical for the interaction of class I with calreticulin. Interestingly, calreticulin displayed sensitivity to class I peptide binding even in TAP-deficient human or mouse cells. Thus, calreticulin is clearly more specific than calnexin in the structures and conformation of the class I molecule with which it can interact.