Basic information
LLPS related evidences
| Publication note | We generated a Drosophila model of FUS toxicity and identified a previously unrecognized synergistic effect between the N-terminal prion-like domain and the C-terminal arginine-rich domain to mediate toxicity. Although the prion-like domain is generally considered to mediate aggregation of FUS, we find that arginine residues in the C-terminal low-complexity domain are also required for maturation of FUS in cellular stress granules. Both WT and mutant FUS could phase separate in the test tube, as indicated by the spontaneous droplet formation. (Organism: Homo sapiens; Cell line: Drosophila melanogaster,U2OS cells,Hela cells) |
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| Material state | liquid,hydrogel : RGG domains are required for efficient binding of the FUS C-terminal domain to phase-separated QGSY hydrogels and liquid droplets. | ||
| LLPS region | 1-526 | Key domains | N-terminal QGSY low-complexity domain,RGG2 domain : FUS requires its two LCDs, both the prion-like QGSY and the arginine-rich RGG2, in cis for toxicity. These LCDs are known to act as binding modules and mediate phase separation of FUS. |
LLPS partner
| Protein partner | _ ( _ ) |
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| RNA partner | _ |
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| Others | _ |
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LLPS regulation
| PTM | _ |
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| Mutation | p.P525L,allRtoG(in RGG2 region) |
Mutating RGG2 increased the dynamics and the fractional recovery of FUS again, and the dynamics of the FUS RGG2 mutant were unaltered compared to those of young SGs. We generated recombinant full-length FUS and a mutant replacing all arginines in RGG2 by glycines. Both WT and mutant FUS could phase separate in the test tube, as indicated by the spontaneous droplet formation. However, the RGG2 mutant did so at dramatically reduced levels. |
| Alternative splicing | _ | |
| Repeat | _ | |
| Oligomerization | _ | |