一个分子组装相位过渡和动态校对调节Ras激活SOS
William Y C Huang1, Steven Alvarez2, Yasushi Kondo1,3,4
1Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Science (New York, N.Y.)
|March 9, 2019
概括
作为Ras激活剂的Sons of Sevenless (SOS) 蛋白在膜结合后表现出激活的延迟. 这种延迟作为动力校对,通过LAT-Grb2-SOS相位过渡来调节.
科学领域:
- 分子和细胞生物学
- 信号传输
- 生物物理
背景情况:
- 七无之子 (SOS) 的关氨酸核酸交换因子 (GEF) 是Ras信号的关键激活剂.
- 在细胞质中SOS是自抑制的,需要膜招募来激活,这个过程涉及结构重组.
- 这种由膜引起的结构变化引入了SOS招募和其催化活性之间的时间延迟.
研究的目的:
- 精确测量SOS单个分子初始膜招募和GEF活动开始之间的时间延迟.
- 研究这种时间延迟在受体介导的Ras激活中的作用.
- 探索LAT-Grb2-SOS复合体形成如何影响膜上的SOS激活动力学.
主要方法:
- 使用Ras功能支持膜的微阵列进行单分子测定.
- 实时观察单个SOS分子以确定从膜招募到GEF活动开始的时间.
- 分析SOS激活时间分布以描述自抑制释放的动力学.
主要成果:
- SOS的激活时间分布呈现出一种典型的上升和下降形状.
- 在膜招募后观察到SOS激活的平均时间大约为50秒.
- 这种动态行为支持Ras激活中的动态校对概念.
- 这种动力校对机制的调节器是LAT-Grb2-SOS光激素驱动的相位过渡.
结论:
- 观察到的SOS激活延迟作为动态校对机制,确保Ras信号的准确性.
- 这种机制通过在等离子膜上形成LAT-Grb2-SOS相分离凝聚物进行微调.
- 了解这些动态可以了解Ras介导的细胞过程的调节.
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