人类无处不在的功能景观
Julian van Gerwen1,2, Maximilian Fottner3, Shengbo Wang4
1Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Switzerland.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
这项研究定义了一个人类的参考泛素,识别了对细胞信号传递至关重要的保存的泛素化部位,而不仅仅是蛋白质降解. 机器学习得分优先考虑功能部位,有助于疾病机制研究.
科学领域:
- 分子生物学分子生物学
- 蛋白质组学是指蛋白质组学.
- 系统生物学 系统生物学
背景情况:
- 蛋白质无化对于细胞过程至关重要,包括蛋白质降解和信号传递.
- 质谱学已经确定了许多无处不在的地点 (ubi-sites),但它们的功能在很大程度上是未知的.
研究的目的:
- 为了创建一个全面的人类参考无处不在.
- 为了确定功能重要和进化保护的ubi-sites.
- 开发用于参与细胞信号传输的功能性ubi-sites的预测得分.
主要方法:
- 协调公共蛋白质组学数据,以建立人类参考无处不在的名称.
- 从多个物种中对准了ubiquitin蛋白质组学数据,以确定保存的ubi-sites.
- 集成的进化,蛋白质和结构特征使用机器学习来创建一个功能性得分.
- 利用扰动蛋白学和化学基因组学进行验证.
主要成果:
- 汇集了108,341个ubi-sites的人类参考无处不在数.
- 确定了进化受约束和超级保护的ubi-sites,通常在监管热点.
- 证明保存的ubi-sites更有可能调节信号,而不是降解.
- 开发了一种基于机器学习的功能评分,用于超过10万个ubi-sites.
- 验证了高得分的ubi-sites的功能相关性,包括一个影响RNA结合.
结论:
- 建立了无处不在名称的系统级原则.
- 为研究蛋白质无化及其在细胞信号传递和疾病中的作用提供了宝贵的资源.
- 强调了保存的ubi-sites在调节蛋白质功能的重要性.
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