通过东部马类脑炎病毒识别VLDLR的结构基础
bioRxiv : the preprint server for biology
|November 28, 2023
概括
东部马脑炎病毒 (EEEV) 和塞米利基森林病毒 (SFV) 结合相同的大脑受体VLDLR,使用不同的尖端蛋白表面. 这揭示了与LDLR相关的蛋白质作为受体的病毒不同的结合模式和低进化障碍.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- 阿尔法病毒是关节动物传播的重要人类病原体.
- 东部马脑炎病毒 (EEEV) 是一种高度毒性的阿尔法病毒,会导致严重的神经病变.
- EEEV和塞米利基森林病毒 (SFV) 使用大脑表达的非常低密度脂蛋白受体 (VLDLR) 和阿波利波蛋白E受体2 (ApoER2) 作为细胞进入受体.
研究的目的:
- 阐明EEEV和SFV与VLDLR结合的结构机制.
- 了解进化上不同的阿尔法病毒如何利用相同的细胞受体.
主要方法:
- 使用单粒子冷电子显微镜 (cryo-EM) 进行了研究.
- 确定了与VLDLR联结域复合的EEEV和SFV尖端糖蛋白的结构.
主要成果:
- EEEV通过其E2糖蛋白子单元上的基本残留物结合VLDLR.
- SFV通过其E1糖蛋白上的两个基本残留物,一个独特的结合部位,参与VLDLR.
- 这些结构显示了VLDLR上的EEEV和SFV的不同的绑定模式.
结论:
- 不同的阿尔法病毒采用不同的分子策略与相同的细胞受体相互作用.
- 灵活的结合模式和与LDLR相关蛋白的小相互作用足迹有助于它们被各种病毒采用为受体.
- 这种适应性表明,病毒获得LDLR家族蛋白质作为细胞受体的进化障碍很低.
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