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PDBsum entry 3e00
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Transcription/DNA
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PDB id
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3e00
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References listed in PDB file
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Key reference
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Title
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Structure of the intact ppar-Gamma-Rxr- Nuclear receptor complex on DNA.
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Authors
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V.Chandra,
P.Huang,
Y.Hamuro,
S.Raghuram,
Y.Wang,
T.P.Burris,
F.Rastinejad.
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Ref.
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Nature, 2008,
456,
350-356.
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PubMed id
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Abstract
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Nuclear receptors are multi-domain transcription factors that bind to DNA
elements from which they regulate gene expression. The peroxisome
proliferator-activated receptors (PPARs) form heterodimers with the retinoid X
receptor (RXR), and PPAR-gamma has been intensively studied as a drug target
because of its link to insulin sensitization. Previous structural studies have
focused on isolated DNA or ligand-binding segments, with no demonstration of how
multiple domains cooperate to modulate receptor properties. Here we present
structures of intact PPAR-gamma and RXR-alpha as a heterodimer bound to DNA,
ligands and coactivator peptides. PPAR-gamma and RXR-alpha form a non-symmetric
complex, allowing the ligand-binding domain (LBD) of PPAR-gamma to contact
multiple domains in both proteins. Three interfaces link PPAR-gamma and
RXR-alpha, including some that are DNA dependent. The PPAR-gamma LBD cooperates
with both DNA-binding domains (DBDs) to enhance response-element binding. The
A/B segments are highly dynamic, lacking folded substructures despite their
gene-activation properties.
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