3DZY

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

3DZY の概要

• エントリーDOI: 10.2210/pdb3dzy/pdb
• 関連するPDBエントリー: 3DZU 3E00
• 分子名称: Retinoic 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)
• 機能のキーワード: dna-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
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : P19793 P37231 Q15596
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 116121.78

構造登録者

Chandra, V.,Huang, P.,Hamuro, Y.,Raghuram, S.,Wang, Y.,Burris, T.P.,Rastinejad, F. (登録日: 2008-07-30, 公開日: 2008-10-28, 最終更新日: 2024-02-21)

主引用文献

Chandra, 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

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

実験手法

X-RAY DIFFRACTION (3.1 Å)