Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM
Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM
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DOI：
10.1038/nsmb.1969
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发表时间：
2011-02-01
影响因子：
16.8
通讯作者：
Yanagi, Yusuke
中科院分区：
文献类型：
--
作者：
Hashiguchi, Takao;Ose, Toyoyuki;Yanagi, Yusuke
麻疹病毒是世界范围内儿童发病和死亡的主要原因，主要利用信号淋巴细胞活化分子（SLAM）作为细胞受体感染免疫细胞。在这里，我们提出了麻疹病毒血凝素（MV-H），受体结合糖蛋白，与SLAM复合物的晶体结构。MV-H头部结构域使用其β-螺旋桨折叠的一侧结合至SLAM的膜远端胞外域的β-折叠。这与其他副粘病毒的附着蛋白不同，其他副粘病毒的附着蛋白使用其β螺旋桨的顶部结合受体。该结构提供了抗病毒药物设计的模板，解释了麻疹病毒疫苗的有效性，以及参与免疫调节的嗜同性SLAM-SLAM相互作用的模型。值得注意的是，所获得的晶体结构显示了MV-H-SLAM四聚体组装（二聚体的二聚体）的两种形式，这可能对融合触发的机制具有影响。
Measles virus, a major cause of childhood morbidity and mortality worldwide, predominantly infects immune cells using signaling lymphocyte activation molecule (SLAM) as a cellular receptor. Here we present crystal structures of measles virus hemagglutinin (MV-H), the receptor-binding glycoprotein, in complex with SLAM. The MV-H head domain binds to a beta-sheet of the membrane-distal ectodomain of SLAM using the side of its beta-propeller fold. This is distinct from attachment proteins of other paramyxoviruses that bind receptors using the top of their beta-propeller. The structure provides templates for antiviral drug design, an explanation for the effectiveness of the measles virus vaccine, and a model of the homophilic SLAM-SLAM interaction involved in immune modulations. Notably, the crystal structures obtained show two forms of the MV-H-SLAM tetrameric assembly (dimer of dimers), which may have implications for the mechanism of fusion triggering.