Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II
Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II
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DOI：
10.1016/s1074-7613(01)00092-9
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发表时间：
2001-01-01
期刊：
影响因子：
32.4
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
--
作者：
Li, YL;Li, HM;Mariuzza, RA
MHC II类分子与细菌超抗原(SAGs)有两个结合位点：铜链上的低亲和力结合部位和β链上的高亲和力锌依赖结合部位。只有前者被定义为结晶学。我们报道了链球菌热原外毒素C(SPE-C)与人类白细胞抗原-DR2a(DRA*0101，DRB5*0101)结合的结构，其中含有髓鞘碱性蛋白(MBP)的自肽。SPE-C通过连接SAG和II类分子的锌桥与β链结合。令人惊讶的是，SPE-C还与MBP多肽进行了广泛的接触，使得多肽占据了MHC分子埋藏在复合物中的三分之一的表面积，类似于TCR-多肽/MHC复合体。因此，SPE-C可能通过模拟传统抗原呈递和识别的多肽依赖来优化T细胞反应。
MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the cu chain and a high-affinity, zinc-dependent site on the beta chain. only the former has been defined crystallographically. We report the structure of streptococcal pyrogenic exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*010l, DRB5*0101) bearing a self-peptide from myelin basic protein (MBP). SPE-C binds the beta chain through a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition.