Polymerization and phase separation of proteins containing low-complexity (LC) domains are important factors in gene expression, mRNA processing and trafficking, and localization of translation. We have used solid-state nuclear magnetic resonance methods to characterize the molecular structure of self-assembling fibrils formed by the LC domain of the fused in sarcoma (FUS) RNA-binding protein. From the 214-residue LC domain of FUS (FUS-LC), a segment of only 57 residues forms the fibril core, while other segments remain dynamically disordered. Unlike pathogenic amyloid fibrils, FUS-LC fibrils lack hydrophobic interactions within the core and are not polymorphic at the molecular structural level. Phosphorylation of core-forming residues by DNA-dependent protein kinase blocks binding of soluble FUS-LC to FUS-LC hydrogels and dissolves phase-separated, liquid-like FUS-LC droplets. These studies offer a structural basis for understanding LC domain self-assembly, phase separation, and regulation by post-translational modification.

中文翻译：

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FUS 蛋白原纤维的结构及其与低复杂性结构域自组装和相分离的相关性。

含有低复杂性 (LC) 结构域的蛋白质的聚合和相分离是基因表达、mRNA 加工和运输以及翻译定位的重要因素。我们使用固态核磁共振方法来表征由肉瘤融合（FUS）RNA结合蛋白的LC结构域形成的自组装原纤维的分子结构。从 FUS (FUS-LC) 的 214 个残基 LC 结构域中，只有 57 个残基的片段形成原纤维核心，而其他片段则保持动态无序。与致病性淀粉样原纤维不同，FUS-LC原纤维在核心内缺乏疏水相互作用，并且在分子结构水平上不具有多态性。DNA 依赖性蛋白激酶对核心形成残基的磷酸化会阻止可溶性 FUS-LC 与 FUS-LC 水凝胶的结合，并溶解相分离的液体状 FUS-LC 液滴。这些研究为理解 LC 结构域自组装、相分离和翻译后修饰调节提供了结构基础。