Structure of FUS Protein Fibrils and Its Relevance to Self-Assembly and Phase Separation of Low-Complexity Domains

Cell. 2017 Oct 19;171(3):615-627.e16. doi: 10.1016/j.cell.2017.08.048. Epub 2017 Sep 21.


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.

Keywords: FUS; amyloid structure; amyotrophic lateral sclerosis; electron microscopy; labile cross-β polymer; liquid droplet; liquid-liquid phase separation; low-complexity sequence; neurodegeneration; solid-state nuclear magnetic resonance.

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphorylation
  • Protein Domains
  • RNA-Binding Protein FUS / chemistry*
  • RNA-Binding Protein FUS / metabolism


  • FUS protein, human
  • RNA-Binding Protein FUS