在CBASS的分子机制上,CapV介导的膜破坏是脂酶效应体CapV的介导
Jianping Kong1, Wanqian Wu1,2, Shiyue Ke1
1State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Nature communications
|September 29, 2025
概括
基于循环寡核酸的抗菌体信号传导系统 (CBASS) 使用像CapV这样的效应剂来触发细菌细胞死亡. 在被3激活时,CapV脂酶会分裂膜脂.
科学领域:
- 细菌学 细菌学是一门学科.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 基于循环寡核酸的抗菌体信号传导系统 (CBASS) 是重要的细菌防御机制.
- 这些系统使用循环核酸激活效应器来诱导宿主细胞死亡,主要是通过膜破坏.
- 帕塔丁类脂酶CapV是许多CBASS通路中的关键效应因子.
研究的目的:
- 阐明一个CBASS效应体CapV诱导膜破坏和细胞死亡的机制.
- 了解CapV在被循环二核酸3'3'-cGAMP激活时发生的结构和形状变化.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定apo-CapV及其复合物的结构.
- 生物化学试验被用来研究CapV的酶活性和膜结合特性.
- 基于细胞的测试被用来观察CapV的局部化和对细菌膜的影响.
主要成果:
- Apo-CapV存在于非活跃的二次和四次状态,具有封闭的脂结合口袋.
- 3'3'-cGAMP的结合会诱导CapV的线程,增强静电膜相互作用,并打开活性部位.
- 已激活的CapV会在细胞极裂开膜脂,导致偏振膜的破坏和细菌的死亡.
结论:
- CapV的激活依赖于导线,涉及由3'3'-cGAMP结合引发的形状变化.
- 这种机制突显出一种新的脂酶介导的细菌抗病毒免疫中的膜破坏策略.
- 这些发现为CBASS功能和细菌防御的分子基础提供了洞察力.
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