洞察通过菌体蛋白调节细菌NADase活性
Hang Yin1,2, Xuzichao Li1,3, Xiaoshen Wang1,3
1State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Key Laboratory of Ocular Trauma, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Nature communications
|March 28, 2024
概括
细菌通过消耗NAD+来使用防御相关的Sirtuin 2 (DSR2) 来防御菌体. 菌体使用DSAD1来抑制DSR2,揭示了一个保存的抗病毒防御机制.
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:
- 沉默信息调节器2 (SIR2) 蛋白质通过消耗尼古丁胺氨酸二核酸 (NAD+) 来调节抗病毒反应.
- 防御相关的Sirtuin 2 (DSR2) 通过NAD+枯竭保护细菌免受菌体感染.
- 菌体使用抗DSR2蛋白1 (DSAD1) 来抵消细菌的防御.
研究的目的:
- 阐明DSR2.2的激活和抑制机制.
- 了解DSR2如何与其激活剂,菌体尾管蛋白 (TTP) 相互作用.
- 调查DSR2结构在其NADase功能中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于在不同状态下确定DSR2结构.
- 生物化学测试以评估NADase活性和抑制.
- 对DSR2-TTP和DSR2-DSAD1相互作用的结构分析.
主要成果:
- DSR2 作为二极体的二极体起作用,需要SIR2 域的四极体化才能产生纳达酶的活性.
- 尾管蛋白 (TTP) 的结合通过打开催化口袋和解域激活DSR2.
- DSAD1通过模仿TTP和阻断TTP结合部位来抑制DSR2.
结论:
- 该研究揭示了TTP激活DSR2和DSAD1.1抑制DSR2的结构基础.
- 这些发现提供了对细菌抗病毒免疫中保存的SIR2-依赖的NAD+耗尽机制的见解.
- 这项工作阐明了细菌防御和菌体逃避策略之间的分子相互作用.
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