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Bingting Ma¹, Ziyi Cao², Weijia Ding¹

¹Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, P.R. China; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Taiyuan 030001, P.R. China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, P.R. China.

|May 22, 2025

概括

西方马类脑炎病毒 (WEEV) 使用细胞受体PCDH10和VLDLR进入. 化-EM结构显示出独特的结合相互作用,包括一个使VLDLR结合成为阿尔法病毒新型模式的VLDLR突变.

科学领域:

病毒学病毒学
结构生物学结构生物学
分子相互作用分子相互作用

背景情况:

西方马脑炎病毒 (WEEV) 是一种阿尔法病毒,通过与特定细胞受体的相互作用感染细胞.
了解这些相互作用对于开发抗病毒策略和理解病毒病原性至关重要.

研究的目的:

阐明WEEV与其细胞受体PCDH10和VLDLR结合的结构机制.
描述这些相互作用中涉及的特定领域和残留物.
调查菌株特异性受体使用的分子基础和受体结合适应的潜力.

主要方法:

低温电子显微镜 (cryo-EM) 用于确定与PCDH10和VLDLR复合的WEEV的高分辨率结构.
细致的病毒包膜蛋白和受体ectodomains的结构分析.
位点定向突变发生,以评估特定突变对受体结合的影响.

主要成果:

冷-EM结构揭示了WEEV如何通过其EC1ectodomain在独特的结合裂中与PCDH10接触.
麦克米兰的WEEV菌株通过多个ecto-LDLR类A (LA) 重复与VLDLR相互作用,N端和C端LA重复具有不同的结合模式.
在E2蛋白中的单一突变 (V265F) 赋予WEEV菌株VLDLR结合能力,而WEEV菌株以前无法结合该受体.
对WEEV观察到的VLDLR结合模式与其他已知的alphavirus不同.

结论:

PCDH10和VLDLR作为WEEV进入的关键受体,具有特定的结构相互作用决定结合.
韦氏病毒在受体结合方面表现出适应性,正如通过单个E2突变获得VLDLR结合所证明的那样.
独特的结合模式突显了阿尔法病毒-受体相互作用的多样性,并提供了对病毒进化和宿主热带主义的见解.

关键词:

CP: 微生物学微生物学在PCDH10中,PCDH10是指PCDH.这就是VLDLRR.西方马类脑炎病毒艾尔法病毒 (alphavirus) 是一种化-EM结构的结构.接收器接收器接收器接收器

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