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

How do intrinsically disordered protein regions encode a driving force for liquid-liquid phase separation?
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DOI:
10.1016/j.sbi.2020.09.004
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发表时间:
2021-04
影响因子:
6.8
通讯作者:
Mittag T
Mittag T
中科院分区:
生物学2区
文献类型:
--
作者:
Borcherds W;Bremer A;Borgia MB;Mittag T

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液-液相分离是生物分子凝聚物形成的机制。无序蛋白质区域通常驱动相分离,但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驱动相分离的混淆。鉴于相分离在许多细胞过程中的关键作用,并且相分离功能障碍可能导致衰弱性疾病,因此了解相行为背后的相互作用和序列特性非常重要。将 IDR 划分为相互作用区域和溶剂化区域的概念框架已被证明特别有用,分析实例化和粗粒度模型可以测试我们对实验相行为驱动力的理解。经过验证的模拟范式能够探索序列空间,帮助我们了解无序蛋白质区域如何编码相行为、哪些 IDR 可能介导细胞中的相分离,以及哪些 IDR 相反高度可溶。
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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