营养感应枢纽GATOR2的结构
Max L Valenstein1,2, Kacper B Rogala3,4,5,6,7, Pranav V Lalgudi8,9
1Whitehead Institute for Biomedical Research, Cambridge, MA, USA. mvalenst@wi.mit.edu.
Nature
|July 13, 2022
概括
对于营养感应和mTORC1激活至关重要的GATOR2复合体已在结构上得到阐明. 这揭示了它的形结构和进化联系, 进步了我们对细胞生长调节的理解.
科学领域:
- 细胞生物学
- 结构生物学
- 生物化学
背景情况:
- 拉巴胺复合体1 (mTORC1) 的机械标调节细胞生长以应对营养.
- 对mTORC1的氨基酸信号包括Rag GTPases,GATOR1和GATOR2.
- 尽管GATOR2在营养感应中的作用,但其结构和生物化学功能以前是未知的.
研究的目的:
- 确定人类GATOR2复合体的三维结构.
- 阐明GATOR2的体积测量和结构.
- 为了解 GATOR2 在 mTORC1 途径中的功能提供结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定人类GATOR2复合物的结构.
- 对GATOR2复合物及其组件进行了生物化学和结构分析.
- 在GATOR2架构中分析了SEH1L和SEC13子单位的整合.
主要成果:
- 人类GATOR2复合体形成了一个大 (1.1 MDa),具有双重对称性的形结构.
- 该综合体具有由WDR24,MIOS和WDR59子单元组成的八角架构,装饰着WD40β螺旋.
- SEH1L和SEC13子单元稳定了脚手架,并暗示了与核孔和膜涂层复合体的进化联系.
- WD40β螺旋与营养传感器SESN2,CASTOR1和GATOR1进行交互.
结论:
- 这项研究揭示了GATOR2复合体的完整结构,
- 确定结构为GATOR2的子单位组织及其与上游监管机构的互动提供了洞察力.
- 这些结构信息作为进一步研究GATOR2在mTORC1信号传递和细胞生长控制中的作用的基础.
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