| Publication note | Here, we investigate the phase separation properties of a class of intrinsically disordered scaffold proteins that we refer to as “FUS family proteins,” because they share similar domain structures, and the first described member of this family was Fused in Sarcoma, or FUS. There are about 30 FUS family proteins in the human genome. . These include FET proteins (FUS and the related proteins EWSR1 and TAF15), TDP-43, and hnRNPA1. (Organism: Homo sapiens; Cell line: _) |
||
|---|---|---|---|
| Material state | liquid,hydrogel : Substitution of glycine for alanine in FUS does not significantly affect the saturation concentration. However, a glycine to alanine (G→A) variant changes the fusion rate of two droplets by more than two orders of magnitude. This suggests that the glycine residues maintain the liquid-like nature of the drops. | ||
| LLPS region | 1-214 | Key domains | low-complexity domain(LCD) : Here we report results from solid state NMR experiments to characterize the molecular structure of fibrils formed by the LC domain of the fused in sarcoma (FUS) RNA-binding protein (FUS-LC). |
| Protein partner | _ ( _ ) |
_ |
|---|---|---|
| RNA partner | _ |
_ |
| Others | _ |
_ |
| PTM | S30/42/54/61/84/87/112/117/131/142,T7/11/19/68;phosphorylation |
Phosphorylation by DNA-PK reduced binding of wild-type FUS-LC: GFP to mCherry:FUS hydrogels by a factor of ten. |
|---|---|---|
| Mutation | p.S84A/S87A,p.T7A/T11A,p.S131A/S142A,p.S112A/S117A,p.T19A/S30A,p.S42A/S54A,p.S30A/S61A,p.S61A/T68A |
Effects of the double Ala substitutions on the ability of DNA-PK to either inhibit hydrogel binding by FUS-LC or melt FUS-LC droplets were correlatively similar. Elimination of phosphorylation sites within the core-forming region identified by solid state NMR (i.e., the S42A/S54A, S61A/T68A, and S42A/S84A mutants) strongly reduced the effects of DNA-PK treatment on both hydrogel binding and droplet formation. By contrast, elimination of phosphorylation sites outside the fibril core (i.e., the T7A/T11A, T19A/S30A, S112A/S117A and S131A/S142A mutants) generally had less impact on the effects of DNA-PK treatment in both assays. |
| Alternative splicing | _ | |
| Repeat | _ | |
| Oligomerization | _ | |