细胞原体免疫系统的目标DNA依赖激活机制SPARTA
Giada Finocchio1, Balwina Koopal2, Ana Potocnik2
1Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland.
Nucleic acids research
|January 15, 2024
概括
斯巴达免疫系统使用一种独特的DNA触发激活机制. 向DNA结合取代了抑制尾巴,使寡合化和NADase活动成为可能.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 收费类受体 (TIR) 域是原核生物和真核生物先天免疫的关键组成部分.
- TIR域作为纳达酶起作用,调节NAD+代谢和信号传递.
- 寡合化对于TIR域催化激活至关重要,但机制在系统之间有所不同.
研究的目的:
- 阐明SPARTA免疫系统激活的结构基础.
- 了解目标DNA介导的寡合化和SPARTA的催化激活的机制.
- 为了提供对SPARTA综合体结构架构的见解.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定SPARTA在非活性和活性状态中的结构.
- 单质和四质SPARTA复合物的结构分析.
- 生物化学测试以调查NADase活性和寡合化.
主要成果:
- 不活跃的单体SPARTA结构显示了一个抑制性的C端尾部占据了核酸结合裂.
- 目标DNA结合将抑制尾部位移,从而诱导pA.go.的结构变化.
- 移位促进了SPARTA二分化,TIR域旋转,合成NADase位点的形成,以及合作性四分化.
结论:
- SPARTA的激活取决于指导RNA介导的目标DNA识别.
- 一种涉及抑制尾部和合作性寡合化的新型机制驱动了催化激活.
- 这项研究揭示了SPARTA的结构复杂性及其依赖DNA的激活途径.
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