Dynamic interaction of the measles virus hemagglutinin with its receptor signaling lymphocytic activation molecule (SLAM, CD150)
Dynamic interaction of the measles virus hemagglutinin with its receptor signaling lymphocytic activation molecule (SLAM, CD150)
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DOI：
10.1074/jbc.m800896200
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发表时间：
2008-04-25
影响因子：
4.8
通讯作者：
Cattaneo, Roberto
中科院分区：
文献类型：
--
作者：
Navaratnarajah, Chanakha K.;Vongpunsawad, Sompong;Cattaneo, Roberto
麻疹病毒与其受体信号转导的淋巴细胞激活分子(SLAM)相互作用，控制细胞进入和控制嗜性。我们预测了麻疹病毒附着蛋白血凝素的潜在界面区域，以开始调查。然后，我们评估了位于这些区域的单个氨基酸与SLAM结合和SLAM依赖的膜融合的相关性，分别通过表面等离子激元共振和受体特异性融合分析来测量。这些研究确定了一种血凝素蛋白残基，异亮氨酸194，它是初级结合所必需的。血凝素蛋白的晶体结构定位于Ile-194在螺旋桨叶片5和6的界面上，我们的数据表明，194残基的小脂肪侧链稳定了有利于结合的蛋白质构象。相反，先前被证明维持SLAM依赖的融合的四个残基并不参与结合。相反，我们的数据证明，在结合后，螺旋桨叶片5上的这四个残基进行受体特异性的构象变化。我们的研究为理解SLAM引起的构象变化在触发融合蛋白展开和膜融合之前如何通过H-蛋白胞外结构域奠定了基础。
The interaction of measles virus with its receptor signaling lymphocytic activation molecule (SLAM) controls cell entry and governs tropism. We predicted potential interface areas of the measles virus attachment protein hemagglutinin to begin the investigation. We then assessed the relevance of individual amino acids located in these areas for SLAM-binding and SLAM-dependent membrane fusion, as measured by surface plasmon resonance and receptor-specific fusion assays, respectively. These studies identified one hemagglutinin protein residue, isoleucine 194, which is essential for primary binding. The crystal structure of the hemagglutinin-protein localizes Ile-194 at the interface of propeller blades 5 and 6, and our data indicate that a small aliphatic side chain of residue 194 stabilizes a protein conformation conducive to binding. In contrast, a quartet of residues previously shown to sustain SLAM-dependent fusion is not involved in binding. Instead, our data prove that after binding, this quartet of residues on propeller blade 5 conducts conformational changes that are receptor-specific. Our study sets a structure-based stage for understanding how the SLAM-elicited conformational changes travel through the H-protein ectodomain before triggering fusion protein unfolding and membrane fusion.