在抑制域 (TOROIDs) 中组织的TORC1调节TORC1活动
Manoël Prouteau1,2, Ambroise Desfosses3, Christian Sieben4,5
1Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.
Nature
|October 5, 2017
概括
葡萄糖吸收迅速使酵母中的拉帕复合物1 (TORC1) 的点失活. 这种无活化涉及TORC1形成称为TOROID的更高阶螺旋结构,由Rag GTPases调节.
科学领域:
- 细胞生物学
- 分子生物学
- 生物化学
背景情况:
- 通过TORC1和TORC2复合体调节细胞生长和新陈代谢.
- 已知GTPase会影响TORC1活动以应对各种信号,但其确切作用尚未完全理解.
研究的目的:
- 通过GTPases在发芽酵母中提取葡萄糖时调节TORC1的机制.
- 阐明TORC1失活的结构基础.
主要方法:
- 超分辨率光学显微镜可视化TORC1的位置.
- 低温电子显微镜和3D重建以确定TORC1组件的结构.
- 基因操纵产生影响TORC1组合和活性的TOR1等位基因.
主要成果:
- 葡萄糖吸收诱导了TORC1的快速,依赖于Rag GTPase的转移到与真空体相关的圆柱形结构中.
- 化EM显示TORC1化成一个空洞的螺旋组合,称为TOROID.
- 在TORC1的寡合化过程中,活性部位被硬质封闭,导致不活化.
- 阻止TOROID形成的特定TOR1突变也阻止了TORC1的失活.
结论:
- 在葡萄糖吸收后的TORC1无活化是由其组装到更高阶的TOROID结构中介导的.
- 拉格GTPases是TORC1组合和随后的失活的关键调节者.
- 蛋白激酶的可逆组合成更高阶结构代表了一种新的调节机制.
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