人类IFIT蛋白对病毒5'-PPP-RNA识别的结构基础
Yazan M Abbas1, Andreas Pichlmair, Maria W Górna
1Department of Biochemistry, Groupe de Recherche Axé sur la Structure des Protéines, McGill University, Montreal, Quebec H3G 0B1, Canada.
Nature
|January 22, 2013
概括
具有四基重复的干扰素诱导蛋白 (IFIT) 直接识别具有5'-三酸盐组 (PPP-RNA) 的病毒RNA. 这种结构洞察力揭示了IFIT如何区分病毒RNA,这对于先天性抗病毒防御至关重要.
科学领域:
- 这是天生的免疫力.
- 分子病毒学分子病毒学.
- 结构生物学是结构生物学.
背景情况:
- 带有四基重复的干扰素诱导蛋白 (IFIT) 是天生的免疫分子.
- 人们认为IFIT通过破坏主机翻译机制来发挥作用.
- 最近的发现表明,IFITs直接识别病毒RNA特征.
研究的目的:
- 阐明IFIT蛋白质对病毒RNA识别的结构基础.
- 了解IFIT如何区分病毒RNA与宿主RNA.
- 研究IFIT介导的抗病毒防御机制.
主要方法:
- 人类IFIT5和IFIT1碎片的X射线晶体学.
- 用5'-三酸RNA (PPP-RNA) 进行复杂形成研究.
- 突变分析,蛋白质分解和凝转移试验.
主要成果:
- 在IFIT5.5中,晶体结构揭示了一个具有正电荷腔的新型螺旋域.
- 这种腔专门结合单链PPP-RNA,使其与RIG-I有所区别.
- PPP-RNA结合是非序列特异性的,需要5'-超悬的~3个核酸.
- 干扰PPP-RNA结合会损害人类胚胎细胞中的抗病毒反应.
结论:
- IFIT蛋白通过专门的结构动机选择性地识别病毒RNA.
- 这种识别机制与其他已知的先天性免疫传感器不同.
- 这些发现为IFIT介导的抗病毒免疫的分子基础提供了洞察力.
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