Sullivan Lucy C, Clements Craig S, Beddoe Travis, Johnson Darryl, Hoare Hilary L, Lin Jie, Huyton Trevor, Hopkins Emma J, Reid Hugh H, Wilce Matthew C J, Kabat Juraj, Borrego Francisco, Coligan John E, Rossjohn Jamie, Brooks Andrew G
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Immunity. 2007 Dec;27(6):900-11. doi: 10.1016/j.immuni.2007.10.013.
The CD94-NKG2 receptor family that regulates NK and T cells is unique among the lectin-like receptors encoded within the natural killer cell complex. The function of the CD94-NKG2 receptors is dictated by the pairing of the invariant CD94 polypeptide with specific NKG2 isoforms to form a family of functionally distinct heterodimeric receptors. However, the structural basis for this selective pairing and how they interact with their ligand, HLA-E, is unknown. We describe the 2.5 A resolution crystal structure of CD94-NKG2A in which the mode of dimerization contrasts with that of other homodimeric NK receptors. Despite structural homology between the CD94 and NKG2A subunits, the dimer interface is asymmetric, thereby providing a structural basis for the preferred heterodimeric assembly. Structure-based sequence comparisons of other CD94-NKG2 family members, combined with extensive mutagenesis studies on HLA-E and CD94-NKG2A, allows a model of the interaction between CD94-NKG2A and HLA-E to be established, in which the invariant CD94 chain plays a more dominant role in interacting with HLA-E in comparison to the variable NKG2 chain.
调节自然杀伤细胞（NK）和T细胞的CD94-NKG2受体家族在自然杀伤细胞复合体中编码的凝集素样受体中是独特的。CD94-NKG2受体的功能取决于不变的CD94多肽与特定NKG2亚型的配对，从而形成一系列功能不同的异二聚体受体。然而，这种选择性配对的结构基础以及它们如何与配体HLA-E相互作用尚不清楚。我们描述了CD94-NKG2A的2.5埃分辨率晶体结构，其中二聚化模式与其他同二聚体NK受体不同。尽管CD94和NKG2A亚基之间存在结构同源性，但二聚体界面是不对称的，从而为优先的异二聚体组装提供了结构基础。对其他CD94-NKG2家族成员进行基于结构的序列比较，结合对HLA-E和CD94-NKG2A的广泛诱变研究，使得能够建立CD94-NKG2A与HLA-E之间相互作用的模型，其中与可变的NKG2链相比，不变的CD94链在与HLA-E相互作用中发挥更主要的作用。
