2QRV

Structure of Dnmt3a-Dnmt3L C-terminal domain complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.259 
  • R-Value Observed: 0.259 

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Literature

Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation.

Jia, D.Jurkowska, R.Z.Zhang, X.Jeltsch, A.Cheng, X.

(2007) Nature 449: 248-251

  • DOI: https://doi.org/10.1038/nature06146
  • Primary Citation of Related Structures:  
    2QRV

  • PubMed Abstract: 

    Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin. DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain. Here we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a-Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a-Dnmt3L interface or the Dnmt3a-Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA-Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing.


  • Organizational Affiliation

    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA (cytosine-5)-methyltransferase 3A
A, D, E, H
295Homo sapiensMutation(s): 0 
Gene Names: DNMT3A
EC: 2.1.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y6K1 (Homo sapiens)
Explore Q9Y6K1 
Go to UniProtKB:  Q9Y6K1
PHAROS:  Q9Y6K1
GTEx:  ENSG00000119772 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y6K1
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA (cytosine-5)-methyltransferase 3-like
B, C, F, G
230Homo sapiensMutation(s): 0 
Gene Names: DNMT3L
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UJW3 (Homo sapiens)
Explore Q9UJW3 
Go to UniProtKB:  Q9UJW3
PHAROS:  Q9UJW3
GTEx:  ENSG00000142182 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UJW3
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.259 
  • R-Value Observed: 0.259 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 401.881α = 90
b = 401.881β = 90
c = 49.689γ = 120
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
PHASESphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description