一个折叠开关调节了阿尔法病毒RNA-依赖RNA聚合酶RNA的构造
Jamie J Arnold1, Sean M Braet2, Luiz C Vieira3
1Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599 USA.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
奥尼翁-尼翁病毒 (ONNV) 依赖RNA的RNA聚合酶 (RdRp,nsP4) 采用了一个不活跃的,扩展的形状. 这种折叠切换对于调节病毒复制和防止免疫激活至关重要.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 阿尔法病毒是蚊子传播的RNA病毒,导致人类重大疾病.
- 依赖RNA的RNA聚合酶 (RdRp,nsP4) 对于阿尔法病毒复制至关重要,但其结构功能关系尚不清楚.
- 之前试图净化活性nsP4衍生物的尝试都没有成功.
研究的目的:
- 在生物化学和生物物理上描述O'nyong-nyong病毒 (ONNV) nsP4.
- 阐明ONNV nsP4活动和监管的结构基础.
- 了解nsP4构造在病毒复制和宿主免疫逃避中的作用.
主要方法:
- 分析超离心法 分析超离心法
- 微角X射线散射 (SAXS) 是一种微角X射线散射技术.
- -交换质谱法 (HDX-MS) 是一种质谱法.
- 人类遗传学分析
主要成果:
- 与计算预测相反,ONNV nsP4存在于需要折叠切换的扩展形状.
- 扩展的nsP4形式表现出较弱的RNA结合,缺乏聚合酶活性.
- 一种前体形式 (CT50-P34) 采用了紧的形状,这表明了调节机制.
- 遗传学分析表明,在紧状态和扩展状态中,残留物都存在保护性.
结论:
- 在ONNV nsP4中,在紧状态 (前身) 和扩展状态 (不活跃) 之间进行调节折叠切换.
- 蛋白质分解裂变激活了复制部位的聚合酶.
- 在RNA合成后,折叠切换到延长,不活跃状态,可以防止细胞质活性和先天免疫反应.
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