通过RIG-I通过ubiquitin介导的抗病毒信号激活的结构基础
Alys Peisley1, Bin Wu1, Hui Xu2
11] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115 USA [2] Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Nature
|March 5, 2014
概括
乌比奎丁链与RIG-I无共价结合.
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:
- 乌比基 (Ub) 传统上以共价方式修改标蛋白,但越来越多地认识到非共价相互作用.
- 天生的免疫传感器RIG-I的信号域 (2CARD) 与K63-连接的泛素链 (K63-Ubn) 相互作用.
- 对2CARD的非共价K63-Ubn结合对于其四聚体形成和下游信号传输至关重要.
研究的目的:
- 阐明K63-Ubn与RIG-I 2CARD的结构基础.
- 了解在RIG-I信号激活中泛胺链相互作用的作用.
- 为了研究共价和非共价乌比奎丁修饰之间的相互作用.
主要方法:
- 人类RIG-I 2CARD四聚合物的X射线结晶学,与K63连接的二-万事素链结合.
- 四重体复合体的结构分析.
- 功能性测试用于评估结合特异性和信号激活.
主要成果:
- 确定了RIG-I 2CARD四合体的晶体结构,采用了"锁洗机"形状.
- K63-Ubn沿着四合体的边缘结合,桥接子单元并稳定结构.
- 结合性激烈性决定了泛素连接和链长特异性;共价泛素进一步稳定了四聚体.
结论:
- 揭示了一种涉及非共价相互作用的全方位介导信号激活机制.
- 突出了 RIG-I 信号传递中共价和非共价泛素结合的协同作用.
- 提供了对RIG-I信号平台的形成和稳定性的结构性见解.
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