The nuclear xenobiotic receptor CAR: Structural determinants of constitutive activation and heterodimerization

Kelly Suino, Li Peng, Ross Reynolds, Yong Li, Ji Young Cha, Joyce J. Repa, Steven A. Kliewer, H. Eric Xu

Research output: Contribution to journalArticle

163 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)893-905
Number of pages13
JournalMolecular cell
Volume16
Issue number6
DOIs
StatePublished - Dec 22 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The nuclear xenobiotic receptor CAR: Structural determinants of constitutive activation and heterodimerization'. Together they form a unique fingerprint.

  • Cite this