4W5A

Complex structure of ATRX ADD bound to H3K9me3S10ph peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.224 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons

Noh, K.M.Maze, I.Zhao, D.Xiang, B.Wenderski, W.Lewis, P.W.Shen, L.Li, H.Allis, C.D.

(2015) Proc Natl Acad Sci U S A 112: 6820-6827

  • DOI: https://doi.org/10.1073/pnas.1411258112
  • Primary Citation of Related Structures:  
    4W5A

  • PubMed Abstract: 

    ATRX (the alpha thalassemia/mental retardation syndrome X-linked protein) is a member of the switch2/sucrose nonfermentable2 (SWI2/SNF2) family of chromatin-remodeling proteins and primarily functions at heterochromatic loci via its recognition of "repressive" histone modifications [e.g., histone H3 lysine 9 tri-methylation (H3K9me3)]. Despite significant roles for ATRX during normal neural development, as well as its relationship to human disease, ATRX function in the central nervous system is not well understood. Here, we describe ATRX's ability to recognize an activity-dependent combinatorial histone modification, histone H3 lysine 9 tri-methylation/serine 10 phosphorylation (H3K9me3S10ph), in postmitotic neurons. In neurons, this "methyl/phos" switch occurs exclusively after periods of stimulation and is highly enriched at heterochromatic repeats associated with centromeres. Using a multifaceted approach, we reveal that H3K9me3S10ph-bound Atrx represses noncoding transcription of centromeric minor satellite sequences during instances of heightened activity. Our results indicate an essential interaction between ATRX and a previously uncharacterized histone modification in the central nervous system and suggest a potential role for abnormal repetitive element transcription in pathological states manifested by ATRX dysfunction.


  • Organizational Affiliation

    Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065;


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transcriptional regulator ATRXA,
C [auth B],
E
129Homo sapiensMutation(s): 2 
Gene Names: ATRXRAD54LXH2
EC: 3.6.4.12
UniProt & NIH Common Fund Data Resources
Find proteins for P46100 (Homo sapiens)
Explore P46100 
Go to UniProtKB:  P46100
PHAROS:  P46100
GTEx:  ENSG00000085224 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP46100
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide from Histone H3.3B [auth C],
D,
F
15Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P84243 (Homo sapiens)
Explore P84243 
Go to UniProtKB:  P84243
PHAROS:  P84243
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP84243
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.224 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.522α = 90
b = 75.522β = 90
c = 137.599γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data collection
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natral Science Foundation of ChinaChina31270763

Revision History  (Full details and data files)

  • Version 1.0: 2015-01-21
    Type: Initial release
  • Version 1.1: 2015-06-17
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description, Source and taxonomy, Structure summary