5W3N

Molecular structure of FUS low sequence complexity domain protein fibrils

Summary for 5W3N

• Entry DOI: 10.2210/pdb5w3n/pdb
• NMR Information: BMRB: 30304
• Descriptor: RNA-binding protein FUS (1 entity in total)
• Functional Keywords: low complexity sequence domain, rna transport, rna granule, intrinsically disordered protein, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 9
• Total formula weight: 223828.61

Authors

Murray, D.T.,Kato, M.,Lin, Y.,Thurber, K.,Hung, I.,McKnight, S.,Tycko, R. (deposition date: 2017-06-08, release date: 2017-09-27, Last modification date: 2024-05-15)

Primary citation

Murray, D.T.,Kato, M.,Lin, Y.,Thurber, K.R.,Hung, I.,McKnight, S.L.,Tycko, R.
Structure of FUS Protein Fibrils and Its Relevance to Self-Assembly and Phase Separation of Low-Complexity Domains.
Cell, 171:615-627.e16, 2017

PubMed Abstract: 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.

PubMed: 28942918
DOI: 10.1016/j.cell.2017.08.048

Experimental method

SOLID-STATE NMR