Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand
Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand
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DOI：
10.1038/45170
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发表时间：
1999-12-09
期刊：
影响因子：
64.8
通讯作者：
Marluzza, RA
中科院分区：
文献类型：
--
作者：
Tormo, J;Natarajan, K;Marluzza, RA
自然杀伤（NK）细胞功能由与靶细胞上的MHC I类（MHC-I）分子相互作用的NK受体调节。鼠NK受体Ly 49 A通过其G型凝集素样NK受体结构域与H-2D（d）相互作用来抑制NK细胞活性。本文报道了Ly 49 A NK受体结构域与未糖基化的H-2D（d）之间复合物的晶体结构。Ly 49 A二聚体在不同位点与两个H-2D（d）分子广泛相互作用。在一个界面处，单个Ly 49 A亚基接触MHC-I肽结合平台的一侧，向H-2D（d）α 2结构域上的保守糖基化位点呈现开放空腔，在第二个较大的界面处，Ly 49 A二聚体结合在与CD 8结合位点重叠的区域中。较小的界面可能代表NK细胞上的Ly 49 A与靶细胞上的MHC-I之间的相互作用，而较大的界面表明Ly 49 A与NK细胞本身上的MHC-I之间的相互作用。MHC-I上的两个Ly 49 A结合位点在空间上与T细胞受体的结合位点不同。
Natural killer (NK) cell function is regulated by NK receptors that interact with MHC class I (MHC-I) molecules on target cells. The murine NK receptor Ly49A inhibits NK cell activity by interacting with H-2D(d) through its G-type-lectin-like NK receptor domain. Here we report the crystal structure of the complex between the Ly49A NK receptor domain and unglycosylated H-2D(d), The Ly49A dimer interacts extensively with two H-2D(d) molecules at distinct sites, At one interface, a single Ly49A subunit contacts one side of the MHC-I peptide-binding platform, presenting an open cavity towards the conserved glycosylation site on the H-2D(d) alpha 2 domain, At a second, larger interface, the Ly49A dimer binds in a region overlapping the CD8-binding site. The smaller interface probably represents the interaction between Ly49A on the NK cell and MHC-I on the target cell, whereas the larger one suggests an interaction between Ly49A and MHC-I on the NK cell itself. Both Ly49A binding sites on MHC-I are spatially distinct from that of the T-cell receptor.