Abstract:
:Phase-separated states of proteins underlie ribonucleoprotein (RNP) granules and nuclear RNA-binding protein assemblies that may nucleate protein inclusions associated with neurodegenerative diseases. We report that the N-terminal low-complexity domain of the RNA-binding protein Fused in Sarcoma (FUS LC) is structurally disordered and forms a liquid-like phase-separated state resembling RNP granules. This state directly binds the C-terminal domain of RNA polymerase II. Phase-separated FUS lacks static structures as probed by fluorescence microscopy, indicating they are distinct from both protein inclusions and hydrogels. We use solution nuclear magnetic resonance spectroscopy to directly probe the dynamic architecture within FUS liquid phase-separated assemblies. Importantly, we find that FUS LC retains disordered secondary structure even in the liquid phase-separated state. Therefore, we propose that disordered protein granules, even those made of aggregation-prone prion-like domains, are dynamic and disordered molecular assemblies with transiently formed protein-protein contacts.
journal_name
Mol Celljournal_title
Molecular cellauthors
Burke KA,Janke AM,Rhine CL,Fawzi NLdoi
10.1016/j.molcel.2015.09.006subject
Has Abstractpub_date
2015-10-15 00:00:00pages
231-41issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(15)00702-9journal_volume
60pub_type
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