关节性阿尔法病毒受体MXRA8与 Chikungunya 病毒包膜蛋白结合的分子基础
Hao Song1, Zhennan Zhao2, Yan Chai3
1Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Cell
|May 14, 2019
概括
奇孔古尼亚病毒 (CHIKV) 使用MXRA8受体进入细胞. 结构研究显示MXRA8与CHIKV结合
科学领域:
- 病毒学和结构生物学
- 病毒进入的分子机制
背景情况:
- 关节病原性阿尔法病毒,包括小孔古尼亚病毒 (CHIKV),由于类风湿性疾病导致全球严重的发病率和经济负担.
- 最近,MXRA8被确定为CHIKV的关键细胞进入受体.
- 了解CHIKV和MXRA8之间的分子相互作用对于开发抗病毒疗法至关重要.
研究的目的:
- 阐明CHIKV与其受体MXRA8的结合的结构基础.
- 为治疗目标识别提供原子层面的互动接口.
主要方法:
- 使用X射线结晶学测定了与CHIKV E蛋白结合的小鼠MXRA8,人类MXRA8以及与人类MXRA8结合的CHIKV病毒样颗粒的结构.
- 低温电子显微镜提供了MXRA8-CHIKV复合物的高分辨率结构数据.
主要成果:
- MXRA8具有两个具有不同结构拓的Ig类域.
- 该受体结合在由CHIKV E蛋白质原体形成的"峡谷"中.
- 原子相互作用涉及MXRA8域和链区域与CHIKV E1-E2残留物,而茎区域对于病毒的进入至关重要.
结论:
- 对MXRA8-CHIKV相互作用的详细结构理解为设计有针对性的抗病毒策略提供了基础.
- 鉴定MXRA8茎区域的关键作用为治疗CHIKV和相关alphavirus提供了一个新的途径.
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