3-DIMENSIONAL STRUCTURE OF A PEPTIDE EXTENDING FROM ONE END OF A CLASS-I MHC BINDING-SITE
3-DIMENSIONAL STRUCTURE OF A PEPTIDE EXTENDING FROM ONE END OF A CLASS-I MHC BINDING-SITE
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DOI：
10.1038/371626a0
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发表时间：
1994-10-13
期刊：
影响因子：
64.8
通讯作者：
WILEY, DC
中科院分区：
文献类型：
--
作者：
COLLINS, EJ;GARBOCZI, DN;WILEY, DC
I 类主要组织相容性复合体 (MHC) 分子将肽呈递给 CD8(+) T 细胞以进行免疫监视（参见参考文献 1）。迄今为止确定的I类MHC分子与八聚体、九聚体和十聚体肽的复合物结构(2-8)显示出共同的结合模式，两个肽末端结合在肽结合位点末端的保守口袋中。长度变化通过中间的肽凸出(5,6) 或之字形(4) 来调节。在这里，我们描述了十聚体肽的结构，该肽与位于肽结合位点外部的羧基末端残基结合。一些蛋白质侧链已重新排列，以允许肽退出。该结构表明甚至更长的肽也可以结合。通过测量复合物对热变性的稳定性来评估改变的结合模式的能量效应。以这种新颖方式结合的肽在生理温度下是稳定的，这引发了关于它们在 T 细胞识别中的作用及其通过蛋白水解加工产生的问题。
CLASS I major histocompatibility complex (MHC) molecules present peptides to CD8(+) T cells for immunological surveillance (reviewed in ref. 1). The structures of complexes of class I MHC molecules with octamer, nonamer and decamer peptides determined until now(2-8) show a common binding mode, with both peptide termini bound in conserved pockets at the ends of the peptide binding site. Length variations were accommodated by the peptide bulging(5,6) or zig-zagging(4) in the middle. Here we describe the structure of a decamer peptide which binds with the carboxy-terminal residue positioned outside the peptide binding site. Several protein side chains have rearranged to allow the peptide to exit. The structure suggests that even longer peptides could bind. The energetic effect of the altered mode of binding has been assessed by measuring the stability of the complex to thermal denaturation. Peptides bound in this novel manner are stable at physiological temperature, raising questions about their role in T-cell recognition and their production by proteolytic processing.