College of Biological Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Center for Computational Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Proteins. 2022 Aug;90(8):1606-1612. doi: 10.1002/prot.26335. Epub 2022 Mar 23.
Intrinsically disordered protein (IDP) plays an important role in liquid-liquid phase separation (LLPS). RNA-binding protein fused in sarcoma (FUS) is a well-studied IDP that induces LLPS since its low-complexity core region (FUS-LC-core) is essential for droplet formation through contacts between FUS-LC-cores. Several experimental studies have reported that adenosine triphosphate (ATP) concentrations modulate LLPS-driven droplet formation through the dissolution of FUS. To elucidate the role of ATP in this dissolution, microsecond-order all-atom molecular dynamics (MD) simulations were performed for a crowded system of FUS-LC-cores in the presence of multiple ATP molecules. Our analysis revealed that the adenine group of ATP frequently contacted the FUS-LC-core, and the phosphoric acid group of ATP was exposed to the external solvent, which promoted both hydration and solubilization of FUS.
无规蛋白（IDP）在液-液相分离（LLPS）中起着重要作用。融合于肉瘤的 RNA 结合蛋白（FUS）是一种研究得很好的 IDP，它可以诱导 LLPS，因为其低复杂度核心区域（FUS-LC-core）通过 FUS-LC-cores 之间的接触对于液滴形成是必不可少的。几项实验研究报告称，三磷酸腺苷（ATP）浓度通过 FUS 的溶解来调节 LLPS 驱动的液滴形成。为了阐明 ATP 在这种溶解中的作用，针对存在多个 ATP 分子的拥挤的 FUS-LC-core 系统进行了微秒级全原子分子动力学（MD）模拟。我们的分析表明，ATP 的腺嘌呤基团经常与 FUS-LC-core 接触，而 ATP 的磷酸基团暴露于外部溶剂中，这促进了 FUS 的水合和溶解。
