细菌DSR2反菌防御系统的菌媒介激活和抑制的结构基础
Jun-Tao Zhang1, Xiao-Yu Liu1, Zhuolin Li1
1Department of Biochemistry, School of Medicine, Southern University of Science and Technology, 518055, Shenzhen, China.
Nature communications
|March 30, 2024
概括
细菌防御相关的Sirtuin 2 (DSR2) 使用NAD+来阻止菌体的传播. 菌体蛋白DSAD1通过阻止菌体尾巴管结合来抑制DSR2,揭示了新的抗菌体防御机制.
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:
- 沉默信息调节器2 (Sir2) 蛋白质是参与NAD+依赖蛋白质脱乙化的酶.
- 防御相关的Sirtuin 2 (DSR2) 是一种细菌Sir2蛋白质,它向菌体尾巴管以抑制菌体的传播.
- 菌体编码的DSR抗防御1 (DSAD1) 对抗DSR2活动,但分子机制尚未完全理解.
研究的目的:
- 阐明通过菌体尾管激活DSR2和通过DSAD1.1抑制DSR2的分子机制.
- 确定DSR2-介导的NAD+枯竭和抗菌素防御的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了DSR2在各种复杂状态中的结构.
- 对于DSR2 Apo形式,DSR2-DSAD1,DSR2-DSAD1-NAD+,DSR2-管和DSR2-管-NAD+复合体的结构分析.
主要成果:
- DSR2存在于四重体形式,具有封闭或开放的C端传感器域 (CTD).
- 单质菌体尾管蛋白与CTD闭合形状结合,激活DSR2进行NAD+水解.
- DSAD1与CTD开放形状结合,以异质抑制尾管结合和DSR2激活.
结论:
- 对DSR2组装,菌体尾管激活和DSAD1.1抑制的结构性见解.
- 在细菌抗菌素防御系统中对NAD+基质催化物的机制理解.
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