Publication Abstract from PubMed
Constitutive androstane receptor (CAR) induces xenobiotic, bilirubin, and thyroid hormone metabolism as a heterodimer with the retinoid X receptor (RXR). Unlike ligand-dependent nuclear receptors, CAR is constitutively active. Here, we report the heterodimeric structure of the CAR and RXR ligand binding domains (LBDs), which reveals an unusually large dimerization interface and a small CAR ligand binding pocket. Constitutive CAR activity appears to be mediated by the compact nature of the CAR LBD that displays several unique features including a shortened AF2 helix and helix H10, which are linked by a two-turn helix that normally adopts an extended loop in other receptors, and an extended helix H2 that stabilizes the canonical LBD fold by packing tightly against helix H3. These structural observations provide a molecular framework for understanding the atypical transcriptional activation properties of CAR.
The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.,Suino K, Peng L, Reynolds R, Li Y, Cha JY, Repa JJ, Kliewer SA, Xu HE Mol Cell. 2004 Dec 22;16(6):893-905. PMID:15610733[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
