Title | Residue-by-Residue View of In Vitro FUS Granules that Bind the C-Terminal Domain of RNA Polymerase II. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Burke KA, Janke AM, Rhine CL, Fawzi NL |
Journal | Mol Cell |
Volume | 60 |
Issue | 2 |
Pagination | 231-41 |
Date Published | 2015 Oct 15 |
ISSN | 1097-4164 |
Keywords | Amino Acid Motifs, Binding Sites, Cytoplasmic Granules, Escherichia coli, Gene Expression, Humans, Intrinsically Disordered Proteins, Molecular Mimicry, Molecular Sequence Data, Phase Transition, Prions, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins, Rheology, RNA, RNA Polymerase II, RNA-Binding Protein FUS, RNA-Binding Proteins |
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. |
DOI | 10.1016/j.molcel.2015.09.006 |
Alternate Journal | Mol. Cell |
PubMed ID | 26455390 |
PubMed Central ID | PMC4609301 |
Grant List | P30GM103410 / GM / NIGMS NIH HHS / United States P20 GM103430 / GM / NIGMS NIH HHS / United States P30 GM103410 / GM / NIGMS NIH HHS / United States P20GM103430 / GM / NIGMS NIH HHS / United States P20 GM104937 / GM / NIGMS NIH HHS / United States S10RR020923 / RR / NCRR NIH HHS / United States P30RR031153 / RR / NCRR NIH HHS / United States P30 RR031153 / RR / NCRR NIH HHS / United States P20GM104937 / GM / NIGMS NIH HHS / United States S10 RR020923 / RR / NCRR NIH HHS / United States S10RR02763 / RR / NCRR NIH HHS / United States P20 RR018728 / RR / NCRR NIH HHS / United States P20RR018728 / RR / NCRR NIH HHS / United States |
Submitted by api_import on December 20, 2019 - 1:39pm