Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex.
Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex.
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DOI：
10.1038/ncomms10356
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发表时间：
2016-01-13
影响因子：
16.6
通讯作者：
Sugita M
中科院分区：
文献类型：
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作者：
Morita D;Yamamoto Y;Mizutani T;Ishikawa T;Suzuki J;Igarashi T;Mori N;Shiina T;Inoko H;Fujita H;Iwai K;Tanaka Y;Mikami B;Sugita M
14-碳饱和脂肪酸（肉豆蔻酸）与氨基末端甘氨酸残基的共价缀合对于某些病毒蛋白质的功能至关重要。这种蛋白质脂化修饰（称为N-肉豆蔻酰化）被特异性识别N-肉豆蔻酰化短肽的宿主细胞毒性T淋巴细胞（CTL）靶向;然而，脂肽抗原（Ag）呈递的分子机制仍然难以捉摸。在这里，我们表明，灵长类动物的主要组织相容性复合体（MHC）I类编码的蛋白能够结合N-豆蔻酰化的5聚体肽，并将它们呈递给特定的CTL。高分辨率的X-射线晶体学分析的MHC I类：脂肽复合物揭示了一个银结合沟，精心构建结合N-豆蔻酰化的短肽，而不是原型9聚体肽。脂肽特异性的，MHC I类限制性CTL的鉴定表明，广泛接受的概念，MHC I类介导的长肽呈递到CTL可能需要一些修改，以纳入一个新的MHC I类功能的脂肽Ag呈递。 近年来，脂质抗原已被添加到抗原库中。在这里，作者已经将Mamu-B*098鉴定为脂肽抗原呈递分子，并且使用结构和生物化学分析表明，它具有与先前分析的蛋白质不同的抗原结合口袋。
The covalent conjugation of a 14-carbon saturated fatty acid (myristic acid) to the amino-terminal glycine residue is critical for some viral proteins to function. This protein lipidation modification, termed N-myristoylation, is targeted by host cytotoxic T lymphocytes (CTLs) that specifically recognize N-myristoylated short peptides; however, the molecular mechanisms underlying lipopeptide antigen (Ag) presentation remain elusive. Here we show that a primate major histocompatibility complex (MHC) class I-encoded protein is capable of binding N-myristoylated 5-mer peptides and presenting them to specific CTLs. A high-resolution X-ray crystallographic analysis of the MHC class I:lipopeptide complex reveals an Ag-binding groove that is elaborately constructed to bind N-myristoylated short peptides rather than prototypic 9-mer peptides. The identification of lipopeptide-specific, MHC class I-restricted CTLs indicates that the widely accepted concept of MHC class I-mediated presentation of long peptides to CTLs may need some modifications to incorporate a novel MHC class I function of lipopeptide Ag presentation. Lipid antigens have been added to the antigenic repertoire in recent years. Here, the authors have identified Mamu-B*098 as a lipopeptide antigen presenting molecule and using structural and biochemical analysis have shown that it has a different antigen binding pocket to previously analysed proteins.