2L3R

NMR structure of UHRF1 Tandem Tudor Domains in a complex with Histone H3 peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Recognition of Multivalent Histone States Associated with Heterochromatin by UHRF1 Protein.

Nady, N.Lemak, A.Walker, J.R.Avvakumov, G.V.Kareta, M.S.Achour, M.Xue, S.Duan, S.Allali-Hassani, A.Zuo, X.Wang, Y.X.Bronner, C.Chedin, F.Arrowsmith, C.H.Dhe-Paganon, S.

(2011) J Biol Chem 286: 24300-24311

  • DOI: https://doi.org/10.1074/jbc.M111.234104
  • Primary Citation of Related Structures:  
    2L3R, 3DB3, 3DB4

  • PubMed Abstract: 

    Histone modifications and DNA methylation represent two layers of heritable epigenetic information that regulate eukaryotic chromatin structure and gene activity. UHRF1 is a unique factor that bridges these two layers; it is required for maintenance DNA methylation at hemimethylated CpG sites, which are specifically recognized through its SRA domain and also interacts with histone H3 trimethylated on lysine 9 (H3K9me3) in an unspecified manner. Here we show that UHRF1 contains a tandem Tudor domain (TTD) that recognizes H3 tail peptides with the heterochromatin-associated modification state of trimethylated lysine 9 and unmodified lysine 4 (H3K4me0/K9me3). Solution NMR and crystallographic data reveal the TTD simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first Tudor subdomain and unmodified H3K4 within a groove between the tandem subdomains. The subdomains undergo a conformational adjustment upon peptide binding, distinct from previously reported mechanisms for dual histone mark recognition. Mutant UHRF1 protein deficient for H3K4me0/K9me3 binding shows altered localization to heterochromatic chromocenters and fails to reduce expression of a target gene, p16(INK4A), when overexpressed. Our results demonstrate a novel recognition mechanism for the combinatorial readout of histone modification states associated with gene silencing and add to the growing evidence for coordination of, and cross-talk between, the modification states of H3K4 and H3K9 in regulation of gene expression.


  • Organizational Affiliation

    Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase UHRF1162Homo sapiensMutation(s): 0 
Gene Names: UHRF1ICBP90NP95RNF106
UniProt & NIH Common Fund Data Resources
Find proteins for Q96T88 (Homo sapiens)
Explore Q96T88 
Go to UniProtKB:  Q96T88
PHAROS:  Q96T88
GTEx:  ENSG00000276043 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96T88
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Histone H311synthetic constructMutation(s): 0 
UniProt
Find proteins for Q3BDD9 (Siphlonella sp. BYU IGCEP083)
Explore Q3BDD9 
Go to UniProtKB:  Q3BDD9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ3BDD9
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
M3L
Query on M3L
B
L-PEPTIDE LINKINGC9 H21 N2 O2LYS
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-08-24
    Changes: Database references
  • Version 1.3: 2020-02-05
    Changes: Data collection, Database references, Derived calculations, Other