5VAB

Crystal structure of ATXR5 PHD domain in complex with histone H3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.179 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.150 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Molecular basis for the methylation specificity of ATXR5 for histone H3.

Bergamin, E.Sarvan, S.Malette, J.Eram, M.S.Yeung, S.Mongeon, V.Joshi, M.Brunzelle, J.S.Michaels, S.D.Blais, A.Vedadi, M.Couture, J.F.

(2017) Nucleic Acids Res 45: 6375-6387

  • DOI: https://doi.org/10.1093/nar/gkx224
  • Primary Citation of Related Structures:  
    5VA6, 5VAB, 5VAC, 5VAH, 5VBC

  • PubMed Abstract: 

    In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases ARABIDOPSIS TRITHORAX RELATED PROTEIN 5 and 6 (ATXR5/6) regulate heterochromatic DNA replication and genome stability. Our initial studies showed that ATXR5/6 discriminate between histone H3 variants and preferentially methylate K27 on H3.1. In this study, we report three regulatory mechanisms contributing to the specificity of ATXR5/6. First, we show that ATXR5 preferentially methylates the R/F-K*-S/C-G/A-P/C motif with striking preference for hydrophobic and aromatic residues in positions flanking this core of five amino acids. Second, we demonstrate that post-transcriptional modifications of residues neighboring K27 that are typically associated with actively transcribed chromatin are detrimental to ATXR5 activity. Third, we show that ATXR5 PHD domain employs a narrow binding pocket to selectively recognize unmethylated K4 of histone H3. Finally, we demonstrate that deletion or mutation of the PHD domain reduces the catalytic efficiency (kcat/Km of AdoMet) of ATXR5 up to 58-fold, highlighting the multifunctional nature of ATXR5 PHD domain. Overall, our results suggest that several molecular determinants regulate ATXR5/6 methyltransferase activity and epigenetic inheritance of H3.1 K27me1 mark in plants.


  • Organizational Affiliation

    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ATXR5 PHD domain58Glycine maxMutation(s): 0 
UniProt
Find proteins for I1N521 (Glycine max)
Explore I1N521 
Go to UniProtKB:  I1N521
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI1N521
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Histone H3 peptideB [auth F]11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P68431 (Homo sapiens)
Explore P68431 
Go to UniProtKB:  P68431
PHAROS:  P68431
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP68431
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.179 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.150 
  • Space Group: P 43 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.01α = 90
b = 44.01β = 90
c = 71.948γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-19
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description