Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea.
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea.
Exp Mol Med. 2022 Sep;54(9):1412-1422. doi: 10.1038/s12276-022-00857-2. Epub 2022 Sep 29.
In this review, we discuss the ways in which recent studies of low-complexity (LC) domains have challenged our understanding of the mechanisms underlying cellular organization. LC sequences, long believed to function in the absence of a molecular structure, are abundant in the proteomes of all eukaryotic organisms. Over the past decade, the phase separation of LC domains has emerged as a fundamental mechanism driving dynamic multivalent interactions of many cellular processes. We review the key evidence showing the role of phase separation of individual proteins in organizing cellular assemblies and facilitating biological function while implicating the dynamics of phase separation as a key to biological validity and functional utility. We also highlight the evidence showing that pathogenic LC proteins alter various phase separation-dependent interactions to elicit debilitating human diseases, including cancer and neurodegenerative diseases. Progress in understanding the biology of phase separation may offer useful hints toward possible therapeutic interventions to combat the toxicity of pathogenic proteins.
在这篇综述中，我们讨论了近期对低复杂度（LC）结构域的研究如何挑战了我们对细胞组织基础机制的理解。LC 序列长期以来被认为在没有分子结构的情况下发挥作用，在所有真核生物的蛋白质组中都很丰富。在过去的十年中，LC 结构域的相分离已成为驱动许多细胞过程的动态多价相互作用的基本机制。我们回顾了关键证据，这些证据表明单个蛋白质的相分离在组织细胞组装和促进生物功能方面的作用，同时暗示相分离的动力学是生物有效性和功能实用性的关键。我们还强调了表明致病 LC 蛋白改变各种依赖相分离的相互作用以引发使人衰弱的人类疾病（包括癌症和神经退行性疾病）的证据。对相分离生物学的理解的进展可能为对抗致病蛋白毒性的可能治疗干预提供有用的线索。
