1XLS

Crystal structure of the mouse CAR/RXR LBD heterodimer bound to TCPOBOP and 9cRA and a TIF2 peptide containg the third LXXLL motifs

Summary for 1XLS

• Entry DOI: 10.2210/pdb1xls/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Orphan nuclear receptor NR1I3, Nuclear receptor coactivator 2, ... (6 entities in total)
• Functional Keywords: lbd, nuclear receptor, car, xenobiotic, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P19793 O35627 Q9WUI9
• Total number of polymer chains: 16
• Total formula weight: 235875.12

Authors

Suino, K.,peng, L.,Reynolds, R.,Li, Y.,Cha, J.-Y.,Repa, J.J.,Kliewer, S.A.,Xu, H.E. (deposition date: 2004-09-30, release date: 2004-12-28, Last modification date: 2024-02-14)

Primary citation

Suino, K.,Peng, L.,Reynolds, R.,Li, Y.,Cha, J.Y.,Repa, J.J.,Kliewer, S.A.,Xu, H.E.
The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.
Mol.Cell, 16:893-905, 2004

PubMed 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.

PubMed: 15610733
DOI: 10.1016/j.molcel.2004.11.036

Experimental method

X-RAY DIFFRACTION (2.96 Å)