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定义了对coproteins的融合凝聚物景观的定义
Swarnendu Tripathi1, Hazheen K Shirnekhi1, Scott D Gorman1,2
1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature communications
|September 28, 2023
概括
超过一半的融合基蛋白 (FO) 形成凝结物,影响癌症. 机器学习预测了广泛的凝结物形成,这表明在基因表达和细胞信号传递中具有不同的功能作用.
科学领域:
- 癌症生物学 癌症生物学
- 生物化学 生物化学
- 分子瘤学分子瘤学
背景情况:
- 融合基蛋白 (FO) 是约17%的癌症的关键驱动因素,通常是由染色体转位引起的.
- 液体-液体相分离 (LLPS) 是一些FO通过异常的生物分子凝聚物形成促进瘤发生的已知机制.
- 在各种FO中,LLPS的流行和功能影响仍然在很大程度上未被探索.
研究的目的:
- 通过融合蛋白 (FO) 调查凝聚物形成的普遍性.
- 描述凝结物形成FO的物理化学性质和功能关联.
- 开发FO凝结行为的预测模型及其对癌症的潜在影响.
主要方法:
- 对166个FO的系统选,以检测HeLa细胞中的冷凝物形成.
- 分析FO的物理化学特征,亚细胞定位和生物功能.
- 开发和应用机器学习模型来预测约3000个额外的FO的凝结行为.
主要成果:
- 58%的经测试的FO形成了冷凝物,与非冷凝物形成物相比,它们表现出明显的物理化学特性.
- 凝聚物形成的FO被按符合亚细胞局部和功能的特征分组.
- 机器学习预测,约3000个FO的67%可能形成凝聚物,35%影响基因表达,47%的非凝聚物形成者与细胞信号相关.
结论:
- 凝结物形成是融合型蛋白质中常见的现象,这表明它在瘤发生过程中起着广泛的作用.
- 不同的功能性作用,特别是在基因表达和细胞信号传递方面,与凝结体阳性和阴性FO有关.
- 开发的预测模型和生成的数据集为未来对FO凝聚和癌症机制的研究提供了宝贵的资源.
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