Abstract
The nuclear receptor PPARγ/RXRα heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazoli-dinediones (TZDs). We report the crystal structures of the PPARγ and RXRα LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PP ARγ agonist rosiglitazone or GI262570, and coactivator peptides. The PPARγ/RXRα heterodimer is asymmetric, with each LBD deviated ~10°from the C2 symmetry, allowing the PPARγ AF-2 helix to interact with helices 7 and 10 of RXRα. The heterodimer interface is composed of conserved motifs in PPARγ and RXRα that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9. The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARγ/RXRα heterodimer by 9cRA.
Original language | English (US) |
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Pages (from-to) | 545-555 |
Number of pages | 11 |
Journal | Molecular cell |
Volume | 5 |
Issue number | 3 |
DOIs | |
State | Published - 2000 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology