6SWG
Crystal structure of the TASOR-Periphilin core complex
Summary for 6SWG
| Entry DOI | 10.2210/pdb6swg/pdb |
| Descriptor | Periphilin-1, Protein TASOR, SULFATE ION (3 entities in total) |
| Functional Keywords | nuclear protein; transcriptional repressor; epigenetic silencing; histone h3 lysine 9 methylation (h3k9me3); transposable element; line1 element; low-complexity sequence; liquid-liquid phase separation (llps); membrane-less compartment; rna-binding protein, gene regulation |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 31657.79 |
| Authors | Prigozhin, D.M.,Freund, S.M.V.,Modis, Y. (deposition date: 2019-09-20, release date: 2020-08-05, Last modification date: 2024-05-15) |
| Primary citation | Prigozhin, D.M.,Douse, C.H.,Farleigh, L.E.,Albecka, A.,Tchasovnikarova, I.A.,Timms, R.T.,Oda, S.I.,Adolf, F.,Freund, S.M.V.,Maslen, S.,Lehner, P.J.,Modis, Y. Periphilin self-association underpins epigenetic silencing by the HUSH complex. Nucleic Acids Res., 48:10313-10328, 2020 Cited by PubMed Abstract: Transcription of integrated DNA from viruses or transposable elements is tightly regulated to prevent pathogenesis. The Human Silencing Hub (HUSH), composed of Periphilin, TASOR and MPP8, silences transcriptionally active viral and endogenous transgenes. HUSH recruits effectors that alter the epigenetic landscape and chromatin structure, but how HUSH recognizes target loci and represses their expression remains unclear. We identify the physicochemical properties of Periphilin necessary for HUSH assembly and silencing. A disordered N-terminal domain (NTD) and structured C-terminal domain are essential for silencing. A crystal structure of the Periphilin-TASOR minimal core complex shows Periphilin forms an α-helical homodimer, bound by a single TASOR molecule. The NTD forms insoluble aggregates through an arginine/tyrosine-rich sequence reminiscent of low-complexity regions from self-associating RNA-binding proteins. Residues required for TASOR binding and aggregation were required for HUSH-dependent silencing and genome-wide deposition of repressive mark H3K9me3. The NTD was functionally complemented by low-complexity regions from certain RNA-binding proteins and proteins that form condensates or fibrils. Our work suggests the associative properties of Periphilin promote HUSH aggregation at target loci. PubMed: 32976585DOI: 10.1093/nar/gkaa785 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.51 Å) |
Structure validation
Download full validation report
