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细菌DSR2抗菌体防御和病毒免疫逃避的分子基础
Jiafeng Huang1,2, Keli Zhu3, Yina Gao4
1Key Laboratory of Molecular Medicine and Biotherapy, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China. jfhuang@ibp.ac.cn.
Nature communications
|May 10, 2024
概括
防御相关的Sirtuin 2 (DSR2) 系统通过耗尽NAD+来保护细菌免受菌体的侵害. 菌体使用DSAD1来抑制DSR2.2. 这项研究揭示了DSR2的冷EM结构,显示了其组装和抑制机制.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 防御相关的Sirtuin 2 (DSR2) 是一种 prokaryotic 系统,提供对菌体感染的防御.
- DSR2通过耗尽细胞内NAD+的功能,诱导流产性感染.
- 菌体编码的DSR抗防御1 (DSAD1) 蛋白质对抗DSR2的活动.
研究的目的:
- 阐明DSR2组装,DSAD1.1.的激活和抑制的结构基础.
- 提供对DSR2介导的抗菌素防御机制的见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了Bacillus subtilis DSR2.2的结构.
- 在apo,Tube-bound和DSAD1-bound状态下解决了结构.
主要成果:
- DSR2 形成一个带有中央 NADase 模块和远端调节模块的长长四聚合物.
- 单质菌体管蛋白与DSR2角结合,形成4:4的DSR2-管复合体,这对NADase活性至关重要.
- DSAD1通过结合到重叠的部位来抑制DSR2,与Tube.com竞争.
结论:
- 这项研究揭示了DSR2防御系统的分子结构.
- 结构洞察力解释了DSR2是如何被菌体管蛋白激活和被DSAD1.1抑制的.
- 这项工作加深了我们对 prokaryotic 抗菌素机制的理解.
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