由病毒RNA激活先天免疫模式识别受体RIG-I的结构基础
Eva Kowalinski1, Thomas Lunardi, Andrew A McCarthy
1European Molecular Biology Laboratory, Grenoble Outstation, France.
Cell
|October 18, 2011
概括
对于天生的免疫力至关重要的RIG-I受体,激活干扰素信号传递. 晶体结构揭示了RNA和ATP结合如何重组RIG-I,释放CARDs进行免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- RIG-I是一种模式识别受体,对天生的免疫力至关重要.
- 它检测到病毒的5'三酸二链RNA (5'ppp-dsRNA) 来触发干扰素的表达.
- RIG-I 具有 N 终端 CARD,一个 DECH 螺旋酶核心和一个 C 终端域 (CTD).
研究的目的:
- 为了阐明RIG-I激活的分子机制.
- 提供对RIG-I.的无体,自抑制和RNA结合状态的结构性见解.
主要方法:
- 使用X射线晶体学来确定RIG-I在不同状态中的结构.
- 结构分析的重点是结合器结合后的形状变化.
主要成果:
- 不活跃的RIG-I采用了与隔离卡片的开放构造.
- ATP和dsRNA的结合会诱导一个封闭的构造,重新排列酶和CTD.
- 酶和CTD在的末端与5'ppp-dsRNA结合,与CARD结合不相容.
结论:
- 提出了一个模型,其中最初的5'ppp-dsRNA与CTD结合,其次是ATP和RNA与螺旋酶结合,释放CARDs.
- 这种机制促进了先天免疫反应下游的信号传递.
- 这些发现增强了对天生的免疫信号酶激活的分子理解.
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