Charge pattern affects the structure and dynamics of polyampholyte condensates
Charge pattern affects the structure and dynamics of polyampholyte condensates
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DOI：
10.1039/d0cp02764b
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发表时间：
2020-09-14
影响因子：
3.3
通讯作者：
Levy, Yaakov
中科院分区：
文献类型：
--
作者：
Hazra, Milan Kumar;Levy, Yaakov
具有内在无序区的蛋白质在体内和体外液-液相分离中都有浓缩的趋势。这种生物分子凝聚体在生物学上重要的调控过程中发挥着各种重要的作用。目前的工作探讨了模型聚两性电解质形成的凝聚体的结构和动态特征，本质上是无序的蛋白质，其带电氨基酸模式不同。带电荷的氨基酸沿着聚两性电解质序列的分布的差异导致密相中明显不同的结构特征，从而导致不同的液体性质。增加的电荷聚集提高了相分离的临界温度，并导致每种聚两性电解质与冷凝物中的相邻蛋白质发生大量的链间接触。因此，具有更大电荷聚集的两性聚电解质采用更扩展的构象，具有高达在稀体相中观察到的两倍的回转半径。液滴内的平移扩散是显著的，仅比本体中慢4-20倍，与致密相中的高构象熵和冷凝物中分子间相互作用网络的高交换速率一致。与更快的扩散相结合，冷凝物也采用更细长的形状，并表现出不完美的填充，这导致空腔。这项研究量化了凝聚体的基本微观性质，包括长程静电力的影响，特别是它们如何被电荷模式调制。
Proteins with intrinsically disordered regions have a tendency to condensatevialiquid-liquid phase separation bothin vitroandin vivo. Such biomolecular coacervates play various significant roles in biologically important regulatory processes. The present work explores the structural and dynamic features of coacervates formed by model polyampholytes, being intrinsically disordered proteins, that differ in terms of their charged amino acid patterns. Differences in the distribution of charged amino acids along the polyampholyte sequence lead to distinctly different structural features in the dense phase and hence to different liquid properties. Increased charge clustering raises the critical temperature for phase separation and results in each polyampholyte experiencing a larger number of inter-chain contacts with neighboring proteins in the condensate. Consequently, polyampholytes with greater charge clustering adopt a much more extended conformation, having a radius of gyration up to twice that observed in the dilute bulk phase. Translational diffusion within the droplet is pronounced, being just 4-20 times slower than in the bulk, consistently with the high conformational entropy in the dense phase and high exchange rate of the network of intermolecular interactions in the condensate. Coupled to the faster diffusion, the condensate also adopts a more elongated shape and exhibits imperfect packing, which results in cavities. This study quantifies the fundamental microscopic properties of condensates including the effect of long-range electrostatic forces and particularly how they can be modulated by the charge pattern.