全长ASC介导炎酶组合的原子机制
Dongmei Xue1,2, Fengyun Ni1, Sheng Liu1
1Multiscale Research Institute for Complex Systems, Fudan University, Shanghai, China.
Nature communications
|November 26, 2025
概括
与亡相关的含有CARD (ASC) 的状蛋白质形成了用于炎症体组装的多轨束. 这些结构对于免疫信号放大和Caspase-1激活至关重要,揭示了ASC丝组织的原子基础.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 含有CARD (ASC) 的斑点状蛋白质对于炎症酶组合至关重要,将模式识别受体与Caspase-1激活联系起来.
- 以前的结构研究仅限于孤立的ASC领域,使得全长ASC的组装机制不清楚.
研究的目的:
- 确定全长ASC丝的原子分辨率结构,阐明炎酶组合的机制.
- 研究ASC结构在Caspase-1激活和免疫信号传递中的作用.
主要方法:
- 原子分辨率冷电子显微镜 (cryo-EM) 的全长ASC丝.
- 低温电子断层扫描 (cryo-ET) 用于更高阶结构分析.
- 在使用野生型和突变ASC的ASC缺乏的THP-1细胞中进行功能性测试.
主要成果:
- 揭示了交替ASCPYD和ASCCARD丝的特征多轨捆绑.
- 在ASCCARD纤维的B端确定了Caspase-1纤维的特定核.
- 证明了域间链接器调节捆绑形成,并且需要完整的捆绑来形成ASC斑点和激活Caspase-1.
结论:
- 该研究定义了全长ASC组装成功能性炎症细胞的结构基础.
- 这些发现突显了ASC多路径捆绑对于有效的免疫信号和Caspase-1激活的重要性.
- ASCb异形的独特结构与减少的炎症酶活性相关.
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