激活NAIP2-NLRC4炎症体的冷EM结构显示核聚合
Liman Zhang1, Shuobing Chen2, Jianbin Ruan1
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
概括
该NAIP-NLRC4炎症体使用单个细菌配体触发多米诺状组合,激活先天免疫力. 这种机制通过单向聚合强化免疫信号.
科学领域:
- 免疫学
- 结构生物学
- 微生物学
背景情况:
- NLR家族的亡抑制蛋白 (NAIP) 是细菌成分的关键传感器.
- 纳伊普可以调用NLRC4炎症酶以启动先天性免疫反应.
- 细菌棒蛋白PrgJ是NAIP的已知配体.
研究的目的:
- 阐明PrgJ-NAIP2-NLRC4炎症体的组装机制.
- 了解腺三酸酶聚合在炎酶激活中的作用.
- 揭示NAIP-NLRC4炎症体中信号放大的结构基础.
主要方法:
- 在亚纳米分辨率下使用冷电子显微镜 (cryo-EM).
- 炎症组复合体的结构重建.
- 蛋白质与蛋白质相互作用和聚合的生物化学分析.
主要成果:
- 通过单向ATPase聚合,PrgJ-NAIP2-NLRC4炎症体形成盘状结构.
- 一个PrgJ激活的NAIP2分子启动了多米诺状的聚合级联.
- 在NLRC4激活时显示了~90°的链旋转.
- 这与Apaf-1光体形成鲜明对比,所有子单元在组装之前都需要连接剂激活.
结论:
- 一个单一的配体激活的NAIP2可以启动大规模的炎症组合.
- NAIP-NLRC4炎症酶利用一种独特的信号放大机制.
- 这项研究提供了对先天免疫感知和激活途径的结构性见解.
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