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PDBsum entry 6e8c
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DNA binding protein/DNA
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PDB id
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6e8c
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PDB id:
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| Name: |
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DNA binding protein/DNA
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Title:
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Crystal structure of the double homeodomain of dux4 in complex with DNA
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Structure:
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Double homeobox protein 4. Chain: a. Fragment: homeobox 1 and 2, residues 16-155. Synonym: double homeobox protein 10. Engineered: yes. DNA (5'- d( Gp Cp Gp Tp Ap Ap Tp Cp Tp Ap Ap Tp Cp Ap Ap Cp A)-3'). Chain: b. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: dux4, dux10. Expressed in: escherichia coli k-12. Expression_system_taxid: 83333. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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2.12Å
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R-factor:
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0.201
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R-free:
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0.247
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Authors:
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J.K.Lee,D.Bosnakovski,E.A.Toso,T.Dinh,S.Banerjee,T.E.Bohl,K.Shi, K.Kurahashi,M.Kyba,H.Aihara
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Key ref:
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J.K.Lee
et al.
(2018).
Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.
Cell Rep,
25,
2955.
PubMed id:
DOI:
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Date:
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27-Jul-18
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Release date:
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26-Dec-18
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PROCHECK
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Headers
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References
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Q9UBX2
(DUX4_HUMAN) -
Double homeobox protein 4 from Homo sapiens
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Seq:
Struc:
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424 a.a.
135 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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G-C-G-T-A-A-T-C-T-A-A-T-C-A-A-C-A
17 bases
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T-G-T-T-G-A-T-T-A-G-A-T-T-A-C-G-C
17 bases
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DOI no:
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Cell Rep
25:2955
(2018)
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PubMed id:
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Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.
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J.K.Lee,
D.Bosnakovski,
E.A.Toso,
T.Dinh,
S.Banerjee,
T.E.Bohl,
K.Shi,
K.Orellana,
M.Kyba,
H.Aihara.
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ABSTRACT
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Double homeobox (DUX) transcription factors are unique to eutherian mammals.
DUX4 regulates expression of repetitive elements during early embryogenesis, but
misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and
translocations overexpressing the DUX4 double homeodomain cause B cell leukemia.
Here, we report the crystal structure of the tandem homeodomains of DUX4 bound
to DNA. The homeodomains bind DNA in a head-to-head fashion, with the linker
making anchoring DNA minor-groove interactions and unique protein contacts.
Remarkably, despite being tandem duplicates, the DUX4 homeodomains recognize
different core sequences. This results from an arginine-to-glutamate mutation,
unique to primates, causing alternative positioning of a key arginine side chain
in the recognition helix. Mutational studies demonstrate that this
primate-specific change is responsible for the divergence in sequence
recognition that likely drove coevolution of embryonically regulated repeats in
primates. Our work provides a framework for understanding the endogenous
function of DUX4 and its role in FSHD and cancer.
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Links
