自动抑制和激活与阿尔戈诺特相关的短TIR-APAZ防御系统的自动抑制和激活
Lijie Guo1,2, Pingping Huang1,2, Zhaoxing Li1,2
1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Nature chemical biology
|November 6, 2023
概括
短 prokaryotic 阿尔戈诺特蛋白质 (pAgos) 防御细菌. 这种细菌可以被杀死. 这项研究揭示了SPARTA,一个pAgo,如何通过结构变化自我抑制和激活,解释了它在细菌防御中的作用.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- Prokaryotic Argonaute 蛋白质 (pAgos) 对于细菌对外来核酸的防御至关重要.
- 众所周知,与TIR-APAZ (SPARTA) 相关的短pAgo在识别目标DNA后可以寡合并耗尽NAD+.
研究的目的:
- 阐明Sparta抑制和激活背后的分子机制.
- 提供结构性洞察力,了解规范SPARTA功能的结构性变化.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定不同状态中的SPARTA结构.
- 生物化学测试以验证功能机制.
主要成果:
- 斯巴达单体是通过一种酸性尾巴自抑制,阻断导向-目标结合通道.
- 目标识别释放了酸性尾巴,诱导了形状变化.
- SPARTA 形成了一个活性四聚合物,具有重新排列的 TIR 域,创建 NADase 活性位点.
结论:
- 结构和生化数据解释了SPARTA的自抑制和激活机制.
- 这项工作扩大了对pAgo介导的细菌防御系统的理解.
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