通过组装介导激活SIR2-HerA超分子复合体,用于抗菌素防御
Zhangfei Shen1, Qingpeng Lin1, Xiao-Yuan Yang2
1Department of Biological Chemistry and Pharmacology, The Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Molecular cell
|December 14, 2023
概括
SIR2-HerA系统使用蛋白质组合来耗尽NAD+并保护细菌免受菌体的侵害. 这种动态复合物切换酶活性,揭示了一种新的抗菌素防御机制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 细菌的抗菌体防御系统对于微生物的生存至关重要.
- SIR2-HerA系统是一个由两种蛋白质组成的复合体,参与细菌对菌体的防御.
- 这种系统在菌体感染时通过耗尽尼古丁胺胺二核酸 (NAD+) 来起作用.
研究的目的:
- 阐明SIR2-HerA复合体的动态组装过程.
- 了解SIR2-HerA.的酶活性和调节.
- 确定SIR2-HerA抗菌素防御机制的结构基础.
主要方法:
- 对SIR2,HerA和SIR2-HerA复合物的生物化学复合.
- 对HerA寡合化状态的分析.
- 电子显微镜 (Cryo-EM) 用于确定高分辨率结构.
- 测试以测量NAD+水解和酶活性.
主要成果:
- HerA表现出动态的寡合化,形成从二元体到非二元体的各种状态.
- 与SIR2的组合诱导了HerA六合体的形成,并将SIR2的活性从核酶切换到NAD+酸酶.
- 高度的ATP抑制了SIR2-HerA复合体的NAD+水解.
- 冷EM揭示了一个大型超分子组合 (高达1MDa) 与SIR2十二相和HerA六相.
- 赫拉六合体在分叉DNA上显示了酶活性.
结论:
- SIR2-HerA复合体利用一种独特的超分子组合来进行抗菌素防御.
- 蛋白质组合动态调节酶活动,切换SIR2的功能.
- 这种机制代表了细菌防御菌体掠食的新策略.
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