Crystal structure of the Ly49I natural killer cell receptor reveals variability in dimerization mode within the Ly49 family.
Crystal structure of the Ly49I natural killer cell receptor reveals variability in dimerization mode within the Ly49 family.
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Ly49I 自然杀伤细胞受体的晶体结构揭示了 Ly49 家族内二聚模式的变异性。
DOI：
10.1016/s0022-2836(02)00498-9
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发表时间：
2002
影响因子：
5.6
通讯作者：
Mariuzza,RoyA
中科院分区：
文献类型：
--
作者：
Dimasi,Nazzareno;Sawicki,MarkW;Reineck,LoraA;Li,Yili;Natarajan,Kannan;Margulies,DavidH;Mariuzza,RoyA
自然杀伤（NK）细胞在先天免疫应答中对病毒感染细胞和肿瘤细胞的检测和破坏起着至关重要的作用。NK细胞的细胞溶解活性是通过NK受体传递的抑制和刺激信号的平衡来调节的，NK受体识别靶细胞上的经典主要组织相容性复合体I类（MHC-I）分子或MHC-I同源物，如MICA。NK受体Ly49家族（Ly49A到W），包括抑制和激活受体，是二聚体II型跨膜糖蛋白，每个亚基由一个c型凝集素样结构域组成，通过一个茎区连接到膜上。我们已经确定了晶体结构，在3.0Å分辨率，小鼠抑制NK受体Ly49I。Ly49I单体与其他c型凝集素样NK受体（包括Ly49A、NKG2D和CD69）的折叠相似。然而，Ly49I单体结合的方式不同于其他NK受体，形成一个更开放的二聚体。因此，Ly49I二聚体的假定mhc结合表面在空间上比Ly49A或NKG2D的相应表面更远。这些结构差异可能反映了Ly49和NKG2D受体识别各自配体的根本不同方式：NKG2D的单个MICA结合位点是由两个单体的精确并列形成的，而每个Ly49单体包含MHC-I的独立结合位点。因此，在Ly49家族中，二聚化几何的结构约束可能相对宽松。这种可变性可能使某些Ly49受体，如Ly49I，以二价结合MHC-I分子，从而稳定受体-配体相互作用，增强向NK细胞的信号传递。
Natural killer (NK) cells play a crucial role in the detection and destruction of virally infected and tumor cells during innate immune responses. The cytolytic activity of NK cells is regulated through a balance of inhibitory and stimulatory signals delivered by NK receptors that recognize classical major histocompatabilty complex class I (MHC-I) molecules, or MHC-I homologs such as MICA, on target cells. The Ly49 family of NK receptors (Ly49A through W), which includes both inhibitory and activating receptors, are homodimeric type II transmembrane glycoproteins, with each subunit composed of a C-type lectin-like domain tethered to the membrane by a stalk region. We have determined the crystal structure, at 3.0Å resolution, of the murine inhibitory NK receptor Ly49I. The Ly49I monomer adopts a fold similar to that of other C-type lectin-like NK receptors, including Ly49A, NKG2D and CD69. However, the Ly49I monomers associate in a manner distinct from that of these other NK receptors, forming a more open dimer. As a result, the putative MHC-binding surfaces of the Ly49I dimer are spatially more distant than the corresponding surfaces of Ly49A or NKG2D. These structural differences probably reflect the fundamentally different ways in which Ly49 and NKG2D receptors recognize their respective ligands: whereas the single MICA binding site of NKG2D is formed by the precise juxtaposition of two monomers, each Ly49 monomer contains an independent binding site for MHC-I. Hence, the structural constraints on dimerization geometry may be relatively relaxed within the Ly49 family. Such variability may enable certain Ly49 receptors, like Ly49I, to bind MHC-I molecules bivalently, thereby stabilizing receptor–ligand interactions and enhancing signal transmission to the NK cell.