3UVL

Crystal structure of WDR5 in complex with the WDR5-interacting motif of MLL3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases.

Zhang, P.Lee, H.Brunzelle, J.S.Couture, J.F.

(2012) Nucleic Acids Res 40: 4237-4246

  • DOI: https://doi.org/10.1093/nar/gkr1235
  • Primary Citation of Related Structures:  
    3UVK, 3UVL, 3UVM, 3UVN, 3UVO

  • PubMed Abstract: 

    In mammals, the SET1 family of lysine methyltransferases (KMTs), which includes MLL1-5, SET1A and SET1B, catalyzes the methylation of lysine-4 (Lys-4) on histone H3. Recent reports have demonstrated that a three-subunit complex composed of WD-repeat protein-5 (WDR5), retinoblastoma-binding protein-5 (RbBP5) and absent, small, homeotic disks-2-like (ASH2L) stimulates the methyltransferase activity of MLL1. On the basis of studies showing that this stimulation is in part controlled by an interaction between WDR5 and a small region located in close proximity of the MLL1 catalytic domain [referred to as the WDR5-interacting motif (Win)], it has been suggested that WDR5 might play an analogous role in scaffolding the other SET1 complexes. We herein provide biochemical and structural evidence showing that WDR5 binds the Win motifs of MLL2-4, SET1A and SET1B. Comparative analysis of WDR5-Win complexes reveals that binding of the Win motifs is achieved by the plasticity of WDR5 peptidyl-arginine-binding cleft allowing the C-terminal ends of the Win motifs to be maintained in structurally divergent conformations. Consistently, enzymatic assays reveal that WDR5 plays an important role in the optimal stimulation of MLL2-4, SET1A and SET1B methyltransferase activity by the RbBP5-ASH2L heterodimer. Overall, our findings illustrate the function of WDR5 in scaffolding the SET1 family of KMTs and further emphasize on the important role of WDR5 in regulating global histone H3 Lys-4 methylation.


  • Organizational Affiliation

    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
WD repeat-containing protein 5318Homo sapiensMutation(s): 0 
Gene Names: WDR5BIG3
UniProt & NIH Common Fund Data Resources
Find proteins for P61964 (Homo sapiens)
Explore P61964 
Go to UniProtKB:  P61964
PHAROS:  P61964
GTEx:  ENSG00000196363 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61964
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-lysine N-methyltransferase MLL311Homo sapiensMutation(s): 2 
EC: 2.1.1.43
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NEZ4 (Homo sapiens)
Explore Q8NEZ4 
Go to UniProtKB:  Q8NEZ4
PHAROS:  Q8NEZ4
GTEx:  ENSG00000055609 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8NEZ4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.98α = 90
b = 86.221β = 90
c = 40.483γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASESphasing
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-14
    Type: Initial release
  • Version 1.1: 2012-02-08
    Changes: Database references
  • Version 1.2: 2012-05-30
    Changes: Database references
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Refinement description