酵母氨基酸感应超级复合体SEAC-EGOC的结构和功能
Lucas Tafur1,2, Lenny Bonadei3, Yiqiang Zheng3
1Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. ltafur@cnio.es.
Nature structural & molecular biology
|February 12, 2026
概括
与Seh1相关的复合体 (SEAC) 将氨基酸信号与细胞生长调节器TORC1.1联系起来. 它的SEACIT子综合体与EGOC结合,作为TORC1调节的关键氨基酸传感枢纽.
科学领域:
- 蜂信号传输是如何进行的
- 细胞生长调节的分子机制
- 氨基酸感知通路的氨基酸感知通路.
背景情况:
- 在哺乳动物中被称为GATOR的Seh1关联复合体 (SEAC) 对于将氨基酸可用性信号转换为拉帕米辛复合体1 (TORC1) 的目标至关重要.
- SEAC包括SEACIT (GATOR1),一种TORC1抑制剂,GTPase激活蛋白 (GAP) 对Gtr1的活性,以及调节SEACIT活动的SEACAT (GATOR2).
- 通过SEACAT调节SEACIT的精确分子机制仍然不完全理解.
研究的目的:
- 使用冷电子显微镜阐明SEAC-EGOC相互作用的结构基础.
- 研究SEAC-EGOC复合体在氨基酸向TORC1.1.信号传输中的功能作用.
- 确定SEACAT内部的关键组件,特别是参与调节TORC1通路激活的Sea2.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定SEAC-EGOC复合物的结构.
- 生物化学测试以评估SEACIT的GTPase激活蛋白 (GAP) 活性.
- 涉及删除子单元 (例如,Sea2) 的遗传研究,以评估对氨基酸对TORC1.1信号传递的影响.
主要成果:
- 低温-EM结构显示,SEACIT直接与SEACAT独立的两个EGOC分子在其活性构造中结合.
- SEACIT的GAP活性对于氨基酸依赖的TORC1调节至关重要,其干扰模仿了Gtr1-Gtr2缺乏的表型.
- 失去Sea2或其N端β螺旋域,显著损害了对TORC1的氨基酸信号传输,这表明它在招募GAP抑制剂中的作用.
结论:
- 该SEAC-EGOC复杂的功能作为一个中心中心,用于检测氨基酸,并将信号传输到TORC1.
- 海洋2β-螺旋域可能通过招募GAP抑制剂来调节TORC1的快速氨基酸信号,同时还涉及其他较慢的调节途径.
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