非平衡策略通过信号受体实现连接体特异性
Andrew Goetz1, Jeremy Barrios2, Ralitsa Radostinova Madsen3
1Department of Biomedical Engineering, Yale University, New Haven, United States.
eLife
|October 29, 2025
概括
受体可以克服热力学极限以达到连接体特异性. 一个新的模型显示多位点酸化和活性降解动力学分类联体,最大限度地提高中间亲和关系的网络活动.
科学领域:
- 生物化学 生物化学
- 系统生物学 系统生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 信号受体与多个连接体相互作用,需要选择性反应.
- 结合体特异性通常受受体-结合体结合亲缘关系在平衡状态限制.
研究的目的:
- 提出一种非平衡模型,解释受体如何实现超越热力学限制的联体特异性.
- 研究多部位酸化和活性受体降解在调节联体特异性的作用.
主要方法:
- 开发一种非平衡模型,包括顺序酸化和活性受体降解.
- 对联体受体复合体的动态分类机制的分析.
- 模拟受体氨酸激酶 (RTK) 信号传递动态.
主要成果:
- 受体降解和多位点酸化协同作用,以控制连接体的特异性.
- 高亲和度复合物被指向降解,低亲和度复合物被指向无活化,限制信号传输.
- 对于具有中间亲缘关系的联体,网络活动是最大化的,这解释了矛盾的实验观测.
结论:
- 动力分类被提出为通过信号受体对连接体进行歧视的一般非平衡策略.
- 这种机制解释了在受体氨酸激酶信号中观察到的非单调信号输出.
- 这些发现凸显了活跃受体降解在细胞信号特异性中的低估的作用.
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