混乱的衰老:与衰老相关的过程中的内在无序的蛋白质
Vladimir D Manyilov1, Nikolay S Ilyinsky2, Semen V Nesterov1,3
1Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutskiy Pereulok, 9, Dolgoprudny, 141700, Russia.
Cellular and molecular life sciences : CMLS
|August 27, 2023
概括
内在无序的蛋白质 (IDP) 和区域 (IDR) 在衰老中至关重要,特别是在DNA调节中. 它们的聚合可能是疾病的信号,并影响细胞健康,为衰老机制提供了新的见解.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 老年学是一门学科.
背景情况:
- 衰老与细胞过程中断有关,这些过程被称为衰老的标志.
- 内在无序的蛋白质 (IDP) 和内在无序的区域 (IDR) 缺乏稳定的结构,使其能够作为信号中心发挥作用.
- 需要进一步阐明IDP/IDR在衰老过程中的具体参与.
研究的目的:
- 调查与衰老相关的蛋白质中IDPs/IDRs的流行率和功能意义.
- 探索IDP/IDR,蛋白质与蛋白质相互作用和衰老特征之间的关联.
- 了解IDP特征作为衰老相关病理的标记物的潜力.
主要方法:
- 从数据库和文献中收集了1702个与衰老相关的蛋白质的数据集.
- 分析了蛋白质疾病含量,基因本体学术语和蛋白质-蛋白质相互作用网络.
- 评估液-液相分离 (LLPS) 的概率和亚细胞局部化.
主要成果:
- IDP/IDR约占与衰老相关的蛋白质数据集的36%,低于人类蛋白质组平均值 (40%).
- 基因实体学分析显示,在约33%的衰老过程中,特别是基因组调节中,IDP/IDR丰富.
- 富含IDP的群显示高LLPS概率,核定位和与DNA相关的功能,与基因组不稳定性,端粒磨损,表观遗传改变和干细胞枯竭有关.
结论:
- IDP/IDR在衰老中起着重要的作用,特别是在与DNA相关的功能中.
- IDP聚合是致病蛋白的潜在标记物,可能对细胞健康有害.
- 了解老化中的IDP行为可能会揭示治疗干预的新策略.
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