8EJO

Crystal structure of the homeodomain of Platypus sDUX in complex with DNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.67 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Antagonism among DUX family members evolved from an ancestral toxic single homeodomain protein.

Bosnakovski, D.Toso, E.A.Ener, E.T.Gearhart, M.D.Yin, L.Luttmann, F.F.Magli, A.Shi, K.Kim, J.Aihara, H.Kyba, M.

(2023) iScience 26: 107823-107823

  • DOI: https://doi.org/10.1016/j.isci.2023.107823
  • Primary Citation of Related Structures:  
    8EJO, 8EJP

  • PubMed Abstract: 

    Double homeobox (DUX) genes are unique to eutherian mammals, expressed transiently during zygotic genome activation (ZGA) and involved in facioscapulohumeral muscular dystrophy (FSHD) and cancer when misexpressed. We evaluate the 3 human DUX genes and the ancestral single homeobox gene sDUX from the non-eutherian mammal, platypus, and find that DUX4 cytotoxicity is not shared with DUXA or DUXB, but surprisingly is shared with platypus sDUX, which binds DNA as a homodimer and activates numerous ZGA genes and long terminal repeat (LTR) elements. DUXA, although transcriptionally inactive, has DNA binding overlap with DUX4, and DUXA-VP64 activates DUX4 targets and is cytotoxic. DUXA competition antagonizes the activity of DUX4 on its target genes, including in FSHD patient cells. Since DUXA is a DUX4 target gene, this competition potentiates feedback inhibition, constraining the window of DUX4 activity. The DUX gene family therefore comprises antagonistic members of opposing function, with implications for their roles in ZGA, FSHD, and cancer.


  • Organizational Affiliation

    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Homeobox domain-containing protein
A, B
71Ornithorhynchus anatinusMutation(s): 0 
UniProt
Find proteins for A0A6I8NF41 (Ornithorhynchus anatinus)
Explore A0A6I8NF41 
Go to UniProtKB:  A0A6I8NF41
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A6I8NF41
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*CP*GP*TP*AP*AP*TP*CP*TP*AP*AP*TP*CP*AP*AP*CP*A)-3')17Homo sapiens
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*TP*GP*TP*TP*GP*AP*TP*TP*AP*GP*AP*TP*TP*AP*CP*GP*C)-3')17Homo sapiens
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
E [auth B]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.67 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.225 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.022α = 90
b = 74.022β = 90
c = 97.309γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
PHENIXphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM124165
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)United StatesAR055685

Revision History  (Full details and data files)

  • Version 1.0: 2023-09-20
    Type: Initial release
  • Version 1.1: 2023-10-04
    Changes: Database references