塞姆利基森林病毒与其受体VLDLR的复合结构
Duanfang Cao1, Bingting Ma2, Ziyi Cao3
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences (CAS), Beijing 100101, China.
Cell
|April 25, 2023
概括
塞姆利基森林病毒 (SFV) 使用非常低密度脂蛋白受体 (VLDLR) 感染. 低温电磁检测显示VLDLR
科学领域:
- 病毒学
- 结构生物学
- 生物化学
背景情况:
- 塞米利克森林病毒 (SFV) 是一种α病毒.
- SFV利用非常低密度脂蛋白受体 (VLDLR) 进入脊椎动物宿主和昆虫载体的细胞.
- 了解这种相互作用的分子基础对于开发抗病毒策略至关重要.
研究的目的:
- 阐明与VLDLR复合的SFV的高分辨率结构.
- 确定SFV和VLDLR之间的特定结合点和相互作用机制.
- 调查VLDLR的LDLR类A (LA) 重复在SFV结合中的作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定SFV-VLDLR复合物的结构.
- 进行结构分析以描述病毒蛋白与VLDLR之间的接口.
- 为了评估不同VLDLR领域的贡献,进行了具有约束力的亲属性研究.
主要成果:
- VLDLR通过其膜-远端LDLR类A (LA) 重复结合到SFV表面的多个E1-DIII位点.
- LA3重复表现出对SFV的最高结合亲和力.
- 相互作用涉及一个小的接口 (378 Å2) 与关键的盐桥构成.
- 连续的LA重复,而不仅仅是单个LA3,通过旋转调整促进协同结合,从而与多个病毒部位相互作用.
结论:
- VLDLR与SFV的结合机制以多个LA重复介导的协同相互作用为特征.
- 这种多价值结合增强了亲和力,并允许来自不同物种的VLDLR结合SFV.
- 这些发现提供了对alphavirus受体相互作用和治疗干预的潜在目标的结构性见解.
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