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3E00

Intact PPAR gamma - RXR alpha Nuclear Receptor Complex on DNA bound with GW9662, 9-cis Retinoic Acid and NCOA2 Peptide

Summary for 3E00
Entry DOI10.2210/pdb3e00/pdb
Related3DZU 3DZY
DescriptorRetinoic acid receptor RXR-alpha, Peroxisome proliferator-activated receptor gamma, DNA (5'-D(*DCP*DAP*DAP*DAP*DCP*DTP*DAP*DGP*DGP*DTP*DCP*DAP*DAP*DAP*DGP*DGP*DTP*DCP*DAP*DG)-3'), ... (8 entities in total)
Functional Keywordsdna-binding, host-virus interaction, metal-binding, nucleus, receptor, transcription, transcription regulation, zinc-finger, activator, diabetes mellitus, disease mutation, obesity, phosphoprotein, transcription-dna complex, transcription/dna
Biological sourceHomo sapiens (Human)
More
Cellular locationNucleus : P19793 P37231 Q15596
Total number of polymer chains6
Total formula weight116041.03
Authors
Chandra, V.,Huang, P.,Hamuro, Y.,Raghuram, S.,Wang, Y.,Burris, T.P.,Rastinejad, F. (deposition date: 2008-07-30, release date: 2008-10-28, Last modification date: 2024-02-21)
Primary citationChandra, V.,Huang, P.,Hamuro, Y.,Raghuram, S.,Wang, Y.,Burris, T.P.,Rastinejad, F.
Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA.
Nature, 456:350-356, 2008
Cited by
PubMed Abstract: 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.
PubMed: 19043829
DOI: 10.1038/nature07413
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.1 Å)
Structure validation

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건을2024-11-06부터공개중

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