与II类主要组织相容性复合体（MHC）结合的SEA变体的晶体结构揭示了SEA交联MHC分子的能力。

Crystal structure of a SEA variant in complex with MHC class II reveals the ability of SEA to crosslink MHC molecules.

作者信息

Petersson Karin, Thunnissen Marjolein, Forsberg Göran, Walse Björn

机构信息

Molecular Biophysics, Centre for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, S-221 00 Lund, Sweden.

出版信息

Structure. 2002 Dec;10(12):1619-26. doi: 10.1016/s0969-2126(02)00895-x.

DOI:10.1016/s0969-2126(02)00895-x

PMID:12467569

Abstract

Although the biological properties of staphylococcal enterotoxin A (SEA) have been well characterized, structural insights into the interaction between SEA and major histocompatibilty complex (MHC) class II have only been obtained by modeling. Here, the crystal structure of the D227A variant of SEA in complex with human MHC class II has been determined by X-ray crystallography. SEA(D227A) exclusively binds with its N-terminal domain to the alpha chain of HLA-DR1. The ability of one SEA molecule to crosslink two MHC molecules was modeled. It shows that this SEA molecule cannot interact with the T cell receptor (TCR) while a second SEA molecule interacts with MHC. Because of its relatively low toxicity, the D227A variant of SEA is used in tumor therapy.

摘要

尽管葡萄球菌肠毒素A（SEA）的生物学特性已得到充分表征，但对SEA与主要组织相容性复合体（MHC）II类之间相互作用的结构认识仅通过建模获得。在此，通过X射线晶体学确定了SEA的D227A变体与人MHC II类复合物的晶体结构。SEA（D227A）仅通过其N端结构域与HLA-DR1的α链结合。模拟了一个SEA分子交联两个MHC分子的能力。结果表明，当第二个SEA分子与MHC相互作用时，该SEA分子不能与T细胞受体（TCR）相互作用。由于SEA的D227A变体毒性相对较低，因此被用于肿瘤治疗。