循环核酸激活CRISPR蛋白酶的抗病毒信号
Christophe Rouillon1,2, Niels Schneberger3, Haotian Chi4
1Institute of Structural Biology, University of Bonn, Bonn, Germany. back2crispr@gmail.com.
Nature
|November 24, 2022
概括
与CRISPR相关的Lon蛋白酶 (CalpL) 裂解CalpT释放CalpS,将外来核酸检测与 prokaryotes 中的转录调节联系起来. 这揭示了CRISPR系统与抗菌体信号之间的联系.
科学领域:
- 微生物学
- 分子生物学
- 结构生物学
背景情况:
- 包括DNA向Cas9和RNA向III类型在内的CRISPR防御系统在原生生物中很常见.
- 在检测异性RNA时,III型CRISPR系统通过循环基酸盐合成启动抗病毒反应.
- 预计与III型系统相关的蛋白质,包括与CRISPR相关的Lon蛋白酶 (CalpL),会结合循环基酸盐.
研究的目的:
- 阐明与CRISPR相关的Lon蛋白酶 (CalpL) 的结构和功能.
- 了解CalpL与CRISPR相关复合体中的其他蛋白质相互作用的机制.
- 建立由CRISPR介导的外来核酸识别与下游监管事件之间的联系.
主要方法:
- 对 CalpL 蛋白的结构分析.
- 生物化学测试以确定 CalpL 在三方复合体中的功能.
- 操作子分析以确定相互作用蛋白 (CalpT和CalpS).
主要成果:
- 与 CalpT 和 CalpS 形成一个稳定的三元复合体.
- 激活的 CalpL 寡合并分裂 CalpT,这是 MazF 的同类物质.
- CalpT的裂变释放了细胞外功能西格玛因子CalpS.
- CalpL 具有 SAVED 域,可以结合循环四基酸盐 (cA4).
结论:
- 这项研究表明,外来核酸的CRISPR检测与转录调节之间存在直接联系.
- 这些发现揭示了CRISPR效应器与SAVED域和基于循环寡核酸的抗菌信号系统之间的联系.
- CalpL的功能突显出一种新型的抗病毒防御和基因调节机制.
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