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在SIR2-HerA系统中协调抗菌体活性的结构基础

Fumeng Liao¹, Guimei Yu¹, Chendi Zhang²

¹State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Cellular Homeostasis and Disease, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

Nucleic acids research

|September 1, 2024

概括

研究人员揭示了细菌抗病毒系统的结构. 这种SIR2 NADase和HerA ATPase/helicase复合体使用NAD+降解和DNA分裂来防御菌体.

科学领域:

细菌学细菌学是一门学科.
结构生物学结构生物学
分子机制的分子机制

背景情况:

发现了一种新型的两基因细菌对菌体的防御系统,涉及SIR2 NADase和HerA ATPase/helicase.
这种细菌SIR2-HerA免疫系统的精确分子机制尚未完全理解.

研究的目的:

阐明细菌SIR2-HerA免疫系统的分子机制.
通过冷电子显微镜 (cryo-EM) 确定SIR2,HerA及其来自Paenibacillus sp.的复合物的结构. 453MF在各种功能状态.

主要方法:

低温电子显微镜 (cryo-EM) 用于确定高分辨率结构.
单个SIR2和HerA蛋白及其组装复合物的结构分析.
生物化学测试用于评估酶活性 (NADase,核酶,ATPase,酶).

主要成果:

这种SIR2蛋白在自抑制状态下形成了十二体环状结构.
赫拉采用独特的分裂螺旋六边形布局,由C端延伸稳定.
SIR2-HerA复合体形成了一个约1.1 MDa的火形结构,对抗菌体活性至关重要.
复杂的形成激活SIR2的NADase/核酶和HerA的ATPase/酶活动.
在绑定 HerA.时,SIR2 从十二摄像头转移到四摄像头.

结论:

这项研究为SIR2和HerA之间的功能通信提供了结构基础.
揭示了一种新的协同抗病毒机制,涉及NAD+降解,ATP水解和DNA裂变.
破坏SIR2-HerA相互作用会显著降低抗菌体活性.

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