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  • Luo, Feng; Gui, Xinrui; Zhou, Heng; Gu, Jinge; Li, Yichen; Liu, Xiangyu; Zhao, Minglei; Li, Dan; Li, Xueming; Liu, Cong

    Nature structural & molecular biology, 04/2018, Letnik: 25, Številka: 4
    Journal Article

    Thermostable cross-β structures are characteristic of pathological amyloid fibrils, but these structures cannot explain the reversible nature of fibrils formed by RNA-binding proteins such as fused in sarcoma (FUS), involved in RNA granule assembly. Here, we find that two tandem (S/G)Y(S/G) motifs of the human FUS low-complexity domain (FUS LC) form reversible fibrils in a temperature- and phosphorylation-dependent manner. We named these motifs reversible amyloid cores, or RAC1 and RAC2, and determined their atomic structures in fibrillar forms, using microelectron and X-ray diffraction techniques. The RAC1 structure features an ordered-coil fibril spine rather than the extended β-strand typical of amyloids. Ser42, a phosphorylation site of FUS, is critical in the maintenance of the ordered-coil structure, which explains how phosphorylation controls fibril formation. The RAC2 structure shows a labile fibril spine with a wet interface. These structures illuminate the mechanism of reversible fibril formation and dynamic assembly of RNA granules.