通过循环核酸激活CBASS Cap5内核酶免疫效应物的活性
Olga Rechkoblit1, Daniela Sciaky2, Dale F Kreitler3
1Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. olga.rechkoblit@mssm.edu.
Nature structural & molecular biology
|February 6, 2024
概括
基于细菌循环寡核酸的抗菌体信号传导系统 (CBASS) 使用像Cap5这样的效应器在病毒感染时触发细胞自杀. 结构研究显示,Cap5激活涉及二聚体到四聚体的转换,使DNA破坏和细菌防御.
科学领域:
- 分子生物学分子生物学
- 细菌学 细菌学是一门学科.
- 结构生物学 结构生物学
背景情况:
- 基于细菌循环寡核酸的抗菌体信号系统 (CBASS) 提供抗病毒防御,类似于人类cGAS-STING通路.
- Cap5是一种流行的CBASS效应器,具有SAVED和HNHDNA内核酶域,对细菌防御至关重要,但其激活机制尚不清楚.
研究的目的:
- 为了阐明Pseudomonas注射器 (Ps) 来自Cap5效应器的激活机制,以响应第二信使结合.
- 为了确定与第二信使复合的全长PsCap5的高分辨率结构.
主要方法:
- 全长版Cap5.5的高分辨率结构分析.
- 生物化学试验用于研究蛋白质构造变化和域相互作用.
主要成果:
- 在第二信使结合时,PsCap5的激活是由二聚体到四聚体的转换驱动的.
- 第二个信使结合诱导了SAVED域的构造变化,为四聚体组装创建了一个平台.
- 这种形状级联重置并激活HNH DNA内核酶域用于DNA裂变.
结论:
- 这项研究揭示了通过结构转换的Cap5介导细菌细胞自杀的分子机制.
- 证明了CBASS系统对抗细菌感染的外部激活的潜力.
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