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PDBsum entry 4mhg
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Transcription/DNA
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PDB id
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4mhg
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PDB id:
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| Name: |
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Transcription/DNA
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Title:
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Crystal structure of etv6 bound to a specific DNA sequence
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Structure:
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Specific 14 bp DNA. Chain: b. Engineered: yes. Complementary specific 14 bp DNA. Chain: c. Engineered: yes. Transcription factor etv6. Chain: a. Fragment: etv6 ets domain, unp residues 329-426.
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Source:
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Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Other_details: custom oligo. Mus musculus. Mouse. Organism_taxid: 10090. Gene: etv6, tel, tel1. Expressed in: escherichia coli.
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Resolution:
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2.20Å
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R-factor:
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0.177
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R-free:
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0.221
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Authors:
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A.C.Chan,S.De,H.J.Coyne Iii,M.Okon,M.E.Murphy,B.J.Graves,L.P.Mcintosh
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Key ref:
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S.De
et al.
(2014).
Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6.
J Mol Biol,
426,
1390-1406.
PubMed id:
DOI:
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Date:
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29-Aug-13
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Release date:
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08-Jan-14
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PROCHECK
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Headers
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References
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P97360
(ETV6_MOUSE) -
Transcription factor ETV6 from Mus musculus
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Seq:
Struc:
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485 a.a.
90 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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A-A-C-C-C-G-G-A-A-G-T-G-A-G
14 bases
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T-C-T-C-A-C-T-T-C-C-G-G-G-T
14 bases
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DOI no:
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J Mol Biol
426:1390-1406
(2014)
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PubMed id:
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Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6.
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S.De,
A.C.Chan,
H.J.Coyne,
N.Bhachech,
U.Hermsdorf,
M.Okon,
M.E.Murphy,
B.J.Graves,
L.P.McIntosh.
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ABSTRACT
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DNA binding by the ETS transcriptional repressor ETV6 (or TEL) is auto-inhibited
~50-fold due to an α-helix that sterically blocks its ETS domain binding
interface. Using NMR spectroscopy, we demonstrate that this marginally stable
helix is unfolded, and not displaced to a non-inhibitory position, when ETV6 is
bound to DNA containing a consensus (5')GGAA(3') recognition site. Although
significantly lower in affinity, binding to non-specific DNA is auto-inhibited
~5-fold and is also accompanied by helix unfolding. Based on NMR chemical shift
perturbations, both specific and non-specific DNA are bound via the same
canonical ETS domain interface. However, spectral perturbations are smaller for
the non-specific complex, suggesting weaker and less well-defined interactions
than in the specific complex. In parallel, the crystal structure of ETV6 bound
to a specific DNA duplex was determined. The structure of this complex reveals
that a non-conserved histidine residue in the ETS domain recognition helix helps
establish the specificity of ETV6 for DNA-binding sites containing
(5')GGAA(3')versus(5')GGAT(3'). These studies provide a unified steric mechanism
for attenuating ETV6 binding to both specific and non-specific DNA and expand
the repertoire of characterized auto-inhibitory strategies utilized to regulate
ETS factors.
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Links
