Complete Phase Diagram for Liquid-Liquid Phase Separation of Intrinsically Disordered Proteins
Complete Phase Diagram for Liquid-Liquid Phase Separation of Intrinsically Disordered Proteins
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DOI：
10.1021/acs.jpclett.9b00099
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发表时间：
2019-04-18
影响因子：
5.7
通讯作者：
Shea, Joan-Emma
中科院分区：
文献类型：
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作者：
McCarty, James;Delaney, Kris T.;Shea, Joan-Emma
许多内在无序的蛋白质已经被证明通过液液相分离自组装成富含蛋白质的相和稀相。所得到的凝聚体可以具有重要的生物学功能，并且形成这些组装体的能力由蛋白质的一级氨基酸序列以及溶液条件决定。我们提出了一个完整的相图的简单凝聚的两性聚电解质本质上无序的蛋白质使用场论模拟方法。我们发现，在初级氨基酸序列和带电荷的氨基酸的分布中的差异沿着序列导致凝聚的相位窗口的差异，与块带电序列具有更大的凝聚窗口比序列与随机图案的电荷。该模型还捕捉了如何改变溶液条件修改相图，可以用来指导实验研究。
A number of intrinsically disordered proteins have been shown to self assemble via liquid liquid phase separation into protein-rich and dilute phases. The resulting coacervates can have important biological functions, and the ability to form these assemblies is dictated by the protein's primary amino acid sequence as well as by the solution conditions. We present a complete phase diagram for the simple coacervation of a polyampholyte intrinsically disordered protein using a field-theoretic simulation approach. We show that differences in the primary amino acid sequence and in the distribution of charged amino acids along the sequence lead to differences in the phase window for coacervation, with block-charged sequences having a larger coacervation window than sequences with a random patterning of charges. The model also captures how changing solution conditions modifies the phase diagram and can serve to guide experimental studies.