对ROS1受体通过NEL/NICOL连接体复合体激活的结构洞察
Weidong An1, Xuewu Zhang2,3, Xiao-Chen Bai4,5
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature communications
|February 24, 2026
概括
受体氨酸激酶ROS1的受体
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 受体氨酸激酶ROS1对于细胞生长和精子成熟至关重要.
- 人们对ROS1的激活机制了解甚少.
研究的目的:
- 为了阐明ROS1.1.的激活机制.
- 确定由其连接体NEL和协同连接体NICOL激活ROS1的结构基础.
主要方法:
- 使用高分辨率冷电子显微镜 (cryo-EM) 来确定ROS1.1的结构.
- 结构分析与生化和功能分析相结合.
主要成果:
- 不结合的ROS1采用弧形形状的形状.
- NEL通过其VWC2域和ROS1的β1域结合ROS1.
- 与NEL结合的NICOL稳定了一个不对称的NEL二元体,招募一个ROS1分子.
- 通过LamG-VWC4相互作用,NEL/NICOL复合体形成寡合体,聚合多个ROS1分子.
- 对于ROS1信号传输,NICOL和NEL/NICOL复杂多元化都至关重要.
结论:
- 尼科尔是ROS1激活的关键辅配体.
- ROS1的激活通过一种独特的联体驱动的寡合化机制发生.
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