Natural selection against protein aggregation on self-interacting and essential proteins in yeast, fly, and worm
Natural selection against protein aggregation on self-interacting and essential proteins in yeast, fly, and worm
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DOI：
10.1093/molbev/msn122
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发表时间：
2008-08-01
影响因子：
10.7
通讯作者：
Dokholyan, Nikolay V.
中科院分区：
文献类型：
--
作者：
Chen, Yiwen;Dokholyan, Nikolay V.
蛋白质聚集是蛋白质自缔合的现象，可能导致对生理的有害影响，这与许多人类疾病如阿尔茨海默病和帕金森病密切相关。尽管在理解蛋白质聚集的机制方面取得了进展，但针对蛋白质聚集的自然选择如何作用于蛋白质复合物的亚基和对生物体适应性具有不同贡献的蛋白质仍然在很大程度上未知。在这里，我们使用实验验证的算法TANGO，并利用酵母，苍蝇和线虫的序列，相互作用和基于表型的功能基因组数据进行全蛋白质组分析。我们发现能够形成同源寡聚体复合物的蛋白质与不起同源寡聚体作用的蛋白质相比具有较低的聚集倾向。此外，与非必需蛋白质相比，对生物体的适应性至关重要的蛋白质具有较低的聚集倾向。我们的研究结果表明，对蛋白质聚集的选择力作用在不同层次的生物系统。
Protein aggregation is the phenomenon of protein self-association potentially leading to detrimental effects on physiology, which is closely related to numerous human diseases such as Alzheimer's and Parkinson's disease. Despite progress in understanding the mechanism of protein aggregation, how natural selection against protein aggregation acts on subunits of protein complexes and on proteins with different contributions to organism fitness remains largely unknown. Here, we perform a proteome-wide analysis by using an experimentally validated algorithm TANGO and utilizing sequence, interactomic and phenotype-based functional genomic data from yeast, fly, and nematode. We find that proteins that are capable of forming homooligomeric complex have lower aggregation propensity compared with proteins that do not function as homooligomer. Further, proteins that are essential to the fitness of an organism have lower aggregation propensity compared with nonessential ones. Our finding suggests that the selection force against protein aggregation acts across different hierarchies of biological system.