6SWG

Crystal structure of the TASOR-Periphilin core complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.230 

wwPDB Validation   3D Report Full Report


This is version 2.4 of the entry. See complete history


Literature

Periphilin self-association underpins epigenetic silencing by the HUSH complex.

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.

(2020) Nucleic Acids Res 48: 10313-10328

  • DOI: https://doi.org/10.1093/nar/gkaa785
  • Primary Citation of Related Structures:  
    6SWG

  • 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.


  • Organizational Affiliation

    Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Periphilin-1
A, B
94Homo sapiensMutation(s): 0 
Gene Names: PPHLN1HSPC206HSPC232
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NEY8 (Homo sapiens)
Explore Q8NEY8 
Go to UniProtKB:  Q8NEY8
PHAROS:  Q8NEY8
GTEx:  ENSG00000134283 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8NEY8
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein TASOR83Homo sapiensMutation(s): 0 
Gene Names: TASORC3orf63FAM208AKIAA1105
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UK61 (Homo sapiens)
Explore Q9UK61 
Go to UniProtKB:  Q9UK61
PHAROS:  Q9UK61
GTEx:  ENSG00000163946 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UK61
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth C]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.57α = 90
b = 93.57β = 90
c = 84.97γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Aimlessdata scaling
CRANK2phasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Wellcome TrustUnited Kingdom101908/Z/13/Z

Revision History  (Full details and data files)

  • Version 1.0: 2020-08-05
    Type: Initial release
  • Version 2.0: 2020-08-12
    Changes: Polymer sequence
  • Version 2.1: 2020-09-16
    Changes: Database references
  • Version 2.2: 2020-10-07
    Changes: Database references
  • Version 2.3: 2020-10-21
    Changes: Database references
  • Version 2.4: 2024-05-15
    Changes: Data collection, Database references, Refinement description