8E4V

Solution structure of the WH domain of MORF


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 1.2 of the entry. See complete history


Literature

MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain.

Becht, D.C.Klein, B.J.Kanai, A.Jang, S.M.Cox, K.L.Zhou, B.R.Phanor, S.K.Zhang, Y.Chen, R.W.Ebmeier, C.C.Lachance, C.Galloy, M.Fradet-Turcotte, A.Bulyk, M.L.Bai, Y.Poirier, M.G.Cote, J.Yokoyama, A.Kutateladze, T.G.

(2023) Nat Commun 14: 697-697

  • DOI: https://doi.org/10.1038/s41467-023-36368-5
  • Primary Citation of Related Structures:  
    8E4V

  • PubMed Abstract: 

    Human acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix (WH) domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the CpG-containing linker DNA and binding of WH2 to the dyad of the nucleosome. The discovery of WHs in MORF and MOZ and their DNA binding functions could open an avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.


  • Organizational Affiliation

    Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isoform 3 of Histone acetyltransferase KAT6B84Homo sapiensMutation(s): 0 
Gene Names: KAT6BKIAA0383MORFMOZ2MYST4
EC: 2.3.1.48
UniProt & NIH Common Fund Data Resources
Find proteins for Q8WYB5 (Homo sapiens)
Explore Q8WYB5 
Go to UniProtKB:  Q8WYB5
PHAROS:  Q8WYB5
GTEx:  ENSG00000156650 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8WYB5
Sequence Annotations
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  • Reference Sequence
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: 2023-05-10
    Type: Initial release
  • Version 1.1: 2023-06-14
    Changes: Other
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references