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TitleStructural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 2006, Year 2019
Publish dateMay 1, 2019
AuthorsXinrui Gui / Feng Luo / Yichen Li / Heng Zhou / Zhenheng Qin / Zhenying Liu / Jinge Gu / Muyun Xie / Kun Zhao / Bin Dai / Woo Shik Shin / Jianhua He / Lin He / Lin Jiang / Minglei Zhao / Bo Sun / Xueming Li / Cong Liu / Dan Li /
PubMed AbstractSubcellular membrane-less organelles consist of proteins with low complexity domains. Many of them, such as hnRNPA1, can assemble into both a polydisperse liquid phase and an ordered solid phase of ...Subcellular membrane-less organelles consist of proteins with low complexity domains. Many of them, such as hnRNPA1, can assemble into both a polydisperse liquid phase and an ordered solid phase of amyloid fibril. The former mirrors biological granule assembly, while the latter is usually associated with neurodegenerative disease. Here, we observe a reversible amyloid formation of hnRNPA1 that synchronizes with liquid-liquid phase separation, regulates the fluidity and mobility of the liquid-like droplets, and facilitates the recruitment of hnRNPA1 into stress granules. We identify the reversible amyloid-forming cores of hnRNPA1 (named hnRACs). The atomic structures of hnRACs reveal a distinct feature of stacking Asp residues, which contributes to fibril reversibility and explains the irreversible pathological fibril formation caused by the Asp mutations identified in familial ALS. Our work characterizes the structural diversity and heterogeneity of reversible amyloid fibrils and illuminates the biological function of reversible amyloid formation in protein phase separation.
External linksNat Commun / PubMed:31043593 / PubMed Central
MethodsX-ray diffraction / EM (electron crystallography)
Resolution0.95 - 1.401 Å
Structure data

PDB-5zgd:
hnRNPA1 reversible amyloid core GFGGNDNFG (residues 209-217) determined by X-ray
Method: X-RAY DIFFRACTION / Resolution: 1.401 Å

PDB-5zgl:
hnRNP A1 segment GGGYGGS (residues 234-240)
Method: X-RAY DIFFRACTION / Resolution: 0.95 Å

PDB-6j60:
hnRNP A1 reversible amyloid core GFGGNDNFG (residues 209-217)
Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 0.96 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN / phase separation / reversibility / phase separation; reversibility / MicroED

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