3DZY: Intact Ppar Gamma - Rxr Alpha Nuclear Receptor Complex On Dna Bound With Rosiglitazone, 9-cis Retinoic Acid And Ncoa2 Peptide

Citation:
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.
PDB ID: 3DZYDownload
MMDB ID: 67636
PDB Deposition Date: 2008/7/30
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3DZY: hexameric; determined by author and by software (PISA)
Molecular Components in 3DZY
Label Count Molecule
Proteins (4 molecules)
1
Retinoic Acid Receptor Rxr-alpha(Gene symbol: RXRA)
Molecule annotation
1
Peroxisome Proliferator-activated Receptor Gamma(Gene symbol: PPARG)
Molecule annotation
2
Ncoa2 Peptide(Gene symbol: NCOA2)
Molecule annotation
Nucleotides(2 molecules)
1
DNA (5'- D(*dcp*dap*dap*dap*dcp*dtp*dap*dgp*dgp*dtp*dcp*dap*dap*dap*dgp*dgp*dt P*dcp*dap*dg)-3')
Molecule annotation
1
DNA (5'- D(*dcp*dtp*dgp*dap*dcp*dcp*dtp*dtp*dtp*dgp*dap*dcp*dcp*dtp*dap*dgp*dt P*dtp*dtp*dg)-3')
Molecule annotation
Chemicals (6 molecules)
1
1
2
4
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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