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-Structure paper
Title | Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 25, Issue 4, Page 341-346, Year 2018 |
Publish date | Apr 2, 2018 |
Authors | Feng Luo / Xinrui Gui / Heng Zhou / Jinge Gu / Yichen Li / Xiangyu Liu / Minglei Zhao / Dan Li / Xueming Li / Cong Liu / |
PubMed Abstract | 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 ...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. |
External links | Nat Struct Mol Biol / PubMed:29610493 |
Methods | X-ray diffraction / EM (electron crystallography) |
Resolution | 0.73 - 1.503 Å |
Structure data | PDB-5xrr: PDB-5xsg: |
Chemicals | ChemComp-ZN: ChemComp-HOH: |
Source |
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Keywords | RNA BINDING PROTEIN / reversible amyloid / hydrous amyloid fibril spine / low complexity domain / RNA granule assembly / cross-coil amyloid fibril / FUS low complexity domain / reversible amyloid fibril |