GATOR1和Rag GTPase异构体之间的冗余静电相互作用驱动了人类细胞中高效的氨基酸传感
Dylan D Doxsey1, Steven D Tettoni1, Shawn B Egri1
1Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
The Journal of biological chemistry
|June 3, 2023
概括
在 GATOR1 的位置上.
科学领域:
- 细胞生物学 细胞生物学
- 营养物质感应的分子机制
- 信号传导途径的信号传导途径.
背景情况:
- 细胞生长和增殖取决于营养的可用性.
- 拉巴胺素复合体1 (mTORC1) 途径的机械性标协调营养感应与细胞生长.
- mTORC1由Rag和Rheb GTPases进行调节,Raga-RagC控制mTORC1的局部化和核酸负载.
研究的目的:
- 为了功能性地描述GATOR1和RagC.之间的相互作用.
- 阐明Depdc5-RagC接口在mTORC1调节中的生物相关性.
- 要了解GATOR1是如何调节Rag GTPase异构体核酸载荷状态的.
主要方法:
- 结构功能分析分析结构功能分析
- 酶动力学测量 酶动力学测量
- 基于细胞的信号分析.
- 低温电子显微镜 (cryo-EM) 结构分析
主要成果:
- 确定了Depdc5 (GATOR1子单元) 和RagC.之间的关键静电相互作用.
- 这种相互作用涉及Depdc5上的Arg-1407和RagC上的负电荷残留物.
- 破坏这种相互作用会损害GATOR1的GTPase激活蛋白 (GAP) 活性和细胞对氨基酸缺失的反应.
结论:
- GATOR1对Rag GTPase异构体的调节是由一个特定的Depdc5-RagC相互作用介导的.
- 这种相互作用对于协调细胞行为与氨基酸可用性至关重要.
- 这些发现为通过营养传感器精确控制mTORC1信号提供了新的见解.
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