论文标题

本质上无序的蛋白质区域如何编码液态液相分离的驱动力?

How do intrinsically disordered protein regions encode a driving force for liquid-liquid phase separation?

论文作者

Borcherds, Wade, Bremer, Anne, Borgia, Madeleine B., Mittag, Tanja

论文摘要

液 - 液相分离是生物分子冷凝物形成的基础机制。无序蛋白质区域通常会驱动相分离,但是无序蛋白质区域的分子相互作用尚不清楚,有时会导致所有无序蛋白质区域都驱动相分离的混合。鉴于相位分离在许多细胞过程中的关键作用,并且相位分离的功能障碍会导致使人衰弱的疾病,因此我们必须了解相互作用的相互作用和序列特性。将IDR分为相互作用和溶剂化区域的概念框架已被证明特别有用,分析的实例和粗粒模型可以测试我们对实验阶段行为的驱动力的理解。经过验证的仿真范式使序列空间探索,以帮助我们理解无序蛋白质区域如何编码相位行为,而IDR可以介导细胞中的相位分​​离,而哪些IDR相反。

Liquid-liquid phase separation is the mechanism underlying the formation of biomolecular condensates. Disordered protein regions often drive phase separation, but molecular interactions of disordered protein regions are not well understood, sometimes leading to the conflation that all disordered protein regions drive phase separation. Given the critical role of phase separation in many cellular processes, and that dysfunction of phase separation can lead to debilitating diseases, it is important that we understand the interactions and sequence properties underlying phase behavior. A conceptual framework that divides IDRs into interacting and solvating regions has proven particularly useful, and analytical instantiations and coarse-grained models can test our understanding of the driving forces against experimental phase behavior. Validated simulation paradigms enable the exploration of sequence space to help our understanding of how disordered protein regions can encode phase behavior, which IDRs may mediate phase separation in cells, and which IDRs are in contrast highly soluble.

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