Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9152, United States; Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9152, United States.
Curr Opin Genet Dev. 2021 Apr;67:111-118. doi: 10.1016/j.gde.2020.12.006. Epub 2021 Jan 14.
Eukaryotic cells express thousands of protein domains long believed to function in the absence of molecular order. These intrinsically disordered protein (IDP) domains are typified by gibberish-like repeats of only a limited number of amino acids that we refer to as domains of low sequence complexity. A decade ago, it was observed that these low complexity (LC) domains can undergo phase transition out of aqueous solution to form either liquid-like droplets or hydrogels. The self-associative interactions responsible for phase transition involve the formation of specific cross-β structures that are unusual in being labile to dissociation. Here we give evidence that the LC domains of two RNA binding proteins, ataxin-2 and TDP43, form cross-β interactions that specify biologically relevant redox sensors.
真核细胞表达数千种蛋白质结构域，这些结构域长期以来被认为在没有分子秩序的情况下发挥作用。这些固有无序的蛋白质（IDP）结构域的特点是只有有限数量的氨基酸组成的类似胡言乱语的重复，我们称之为低序列复杂度结构域。十年前，人们观察到这些低复杂度（LC）结构域可以在离开水相的情况下发生相变，形成类似液体的液滴或水凝胶。负责相变的自缔合相互作用涉及到形成特定的交叉-β结构，这些结构在解离方面不稳定，这在通常情况下是不常见的。在这里，我们提供的证据表明，两种 RNA 结合蛋白，ataxin-2 和 TDP43 的 LC 结构域形成交叉-β相互作用，指定了具有生物学相关性的氧化还原传感器。
