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PDBsum entry 4umm
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Nuclear receptor
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PDB id
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4umm
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Contents |
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78 a.a.
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87 a.a.
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241 a.a.
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236 a.a.
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References listed in PDB file
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Key reference
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Title
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The palindromic DNA-Bound usp/ecr nuclear receptor adopts an asymmetric organization with allosteric domain positioning.
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Authors
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M.Maletta,
I.Orlov,
P.Roblin,
Y.Beck,
D.Moras,
I.M.Billas,
B.P.Klaholz.
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Ref.
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Nat Commun, 2014,
5,
4139.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Nuclear receptors (NRs) regulate gene expression through DNA- and ligand-binding
and thus represent crucial therapeutic targets. The ultraspiracle
protein/ecdysone receptor (USP/EcR) complex binds to half-sites with a one base
pair spaced inverted repeat (IR1), a palindromic DNA response element (RE)
reminiscent of IRs observed for vertebrate steroid hormone receptors. Here we
present the cryo electron microscopy structure of the USP/EcR complex bound to
an IR1 RE which provides the first description of a full IR-bound NR complex.
The structure reveals that even though the DNA is almost symmetric, the complex
adopts a highly asymmetric architecture in which the ligand-binding domains
(LBDs) are positioned 5' off-centred. Additional interactions of the USP LBD
with the 5'-flanking sequence trigger transcription activity as monitored by
transfection assays. The comparison with DR-bound NR complexes suggests that DNA
is the major allosteric driver in inversely positioning the LBDs, which serve as
the main binding-site for transcriptional regulators.
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