病毒的帽子捕获和转录的结构快照
Harry M Williams1,2,3, Sigurdur R Thorkelsson2,3,4, Dominik Vogel1
1Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Germany.
Nucleic acids research
|May 6, 2024
概括
严重发烧与血小板缺血综合征病毒 (SFTSV) 使用其大 (L) 蛋白来窃取宿主mRNA盖子进行转录. 结构研究揭示了L蛋白.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 严重发烧与血小板缺血综合征病毒 (SFTSV) 是东亚流行的一种新兴传染病.
- SFTSV大 (L) 蛋白对于病毒转录至关重要,它利用一个捕获帽子机制来获取宿主mRNA片段.
- 了解L蛋白的功能对于开发抗病毒策略至关重要.
研究的目的:
- 为了阐明由SFTSV L蛋白质捕获帽子的机制.
- 为了确定SFTSV L蛋白在转录相关状态中的结构.
- 研究宿主mRNA纳入病毒转录的结构基础.
主要方法:
- 开发一个体外摘帽试验.
- 高分辨率电子冷显微镜 (cryo-EM) 用于确定蛋白质结构.
- 在体外生化测试和基于细胞的实验.
主要成果:
- 获得了SFTSV L蛋白质的三种高质量的冷EM结构,捕捉了原始化和早期延长状态.
- 一个结构揭示了与L蛋白的cap-binding域 (CBD) 结合的封闭RNA,其构成为RNA依赖RNA聚合酶 (RdRp) 活性.
- 观察到,在原料扩展的初始阶段,原料构造保持在原料扩展的初始阶段.
结论:
- 这项研究为SFTSV L蛋白质的捕获机制提供了前所未有的结构洞察力.
- 这些发现澄清了SFTSV和相关的bunyaviruses如何劫持宿主mRNA进行病毒转录.
- 这项研究推进了对病毒RNA合成和宿主-病原体相互作用的机制理解.
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