1XV9

crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid, and 5b-pregnane-3,20-dione.

Summary for 1XV9

• Entry DOI: 10.2210/pdb1xv9/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Orphan nuclear receptor NR1I3, nuclear receptor coactivator 1 isoform 1, ... (6 entities in total)
• Functional Keywords: car, rxr, src1, pregnanedione, dna binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q14994 P19793
• Total number of polymer chains: 8
• Total formula weight: 116914.26

Authors

Xu, R.X.,Lambert, M.H.,Wisely, B.B.,Warren, E.N.,Weinert, E.E.,Waitt, G.M.,Williams, J.D.,Moore, L.B.,Willson, T.M.,Moore, J.T. (deposition date: 2004-10-27, release date: 2004-12-28, Last modification date: 2024-02-14)

Primary citation

Xu, R.X.,Lambert, M.H.,Wisely, B.B.,Warren, E.N.,Weinert, E.E.,Waitt, G.M.,Williams, J.D.,Collins, J.L.,Moore, L.B.,Willson, T.M.,Moore, J.T.
A Structural Basis for Constitutive Activity in the Human CAR/RXRalpha Heterodimer.
Mol.Cell, 16:919-928, 2004

PubMed Abstract: The X-ray crystal structure of the human constitutive androstane receptor (CAR, NR1I3)/retinoid X receptor alpha (RXRalpha, NR2B1) heterodimer sheds light on the mechanism of ligand-independent activation of transcription by nuclear receptors. CAR contains a single-turn Helix X that restricts the conformational freedom of the C-terminal AF2 helix, favoring the active state of the receptor. Helix X and AF2 sit atop four amino acids that shield the CAR ligand binding pocket. A fatty acid ligand was identified in the RXRalpha binding pocket. The endogenous RXRalpha ligand, combined with stabilizing interactions from the heterodimer interface, served to hold RXRalpha in an active conformation. The structure suggests that upon translocation, CAR/RXRalpha heterodimers are preorganized in an active conformation in cells such that they can regulate transcription of target genes. Insights into the molecular basis of CAR constitutive activity can be exploited in the design of inverse agonists as drugs for treatment of obesity.

PubMed: 15610735
DOI: 10.1016/j.molcel.2004.11.042

Experimental method

X-RAY DIFFRACTION (2.7 Å)