据研究人员介绍，低序列复杂性的蛋白质结构域不会折叠成稳定的三维结构。然而，具有这些序列的蛋白质有助于细胞组织的许多方面，包括没有被膜包围的核和细胞质结构的组装。这些细胞组装的动态性质是由低复杂性结构域（LCD）通过不稳定、交叉β结构瞬时自聚集的能力造成的。在过去的十年中，有助于研究LCD自结合的机制研究已经发展到了相分离的简单检测形式。
研究人员用这种检测方法证明了负责LCD自聚集的相互作用可以由接近折叠和未折叠状态之间平衡的有争议的蛋白质结构所决定。此外，导致Charcot-Marie-Tooth病、额颞叶痴呆症和阿尔茨海默病的错义突变在体外和培养的细胞系统中表现出它们的病理生理学，即增强LCD自聚集时形成的其他不稳定分子结构的稳定性。
附：英文原文
Title: Mutations linked to neurological disease enhance self-association of low-complexity protein sequences
Author: Xiaoming Zhou, Lily Sumrow, Kyuto Tashiro, Lillian Sutherland, Daifei Liu, Tian Qin, Masato Kato, Glen Liszczak, Steven L. McKnight
Issue&Volume: 2022-07-01
Abstract: Protein domains of low sequence complexity do not fold into stable, three-dimensional structures. Nevertheless, proteins with these sequences assist in many aspects of cell organization, including assembly of nuclear and cytoplasmic structures not surrounded by membranes. The dynamic nature of these cellular assemblies is caused by the ability of low-complexity domains (LCDs) to transiently self-associate through labile, cross-β structures. Mechanistic studies useful for the study of LCD self-association have evolved over the past decade in the form of simple assays of phase separation. Here, we have used such assays to demonstrate that the interactions responsible for LCD self-association can be dictated by labile protein structures poised close to equilibrium between the folded and unfolded states. Furthermore, missense mutations causing Charcot-Marie-Tooth disease, frontotemporal dementia, and Alzheimer’s disease manifest their pathophysiology in vitro and in cultured cell systems by enhancing the stability of otherwise labile molecular structures formed upon LCD self-association.
DOI: abn5582
Source: https://www.science.org/doi/10.1126/science.abn5582