Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid.
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Egea PF, Mitschler A, Rochel N, Ruff M, Chambon P, Moras D
Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid.
EMBO J. 2000 Jun 1;19(11):2592-601.
- PubMed ID
- 10835357 [ View in PubMed]
- Abstract
The pleiotropic effects of active retinoids are transduced by their cognate nuclear receptors, retinoid X receptors (RXRs) and retinoic acid receptors (RARs), which act as transcriptional regulators activated by two stereoisomers of retinoic acid (RA): 9-cis RA (9-cRA) and all-trans RA (a-tRA). Among nuclear receptors, RXR occupies a central position and plays a crucial role in many intracellular signalling pathways as a ubiquitous heterodimerization partner with numerous other members of this superfamily. Whereas RARs bind both isomers, RXRs exclusively bind 9-cRA. The crystal structure of the ligand-binding domain (LBD) of human RXRalpha bound to 9-cRA reveals the molecular basis of this ligand selectivity and allows a comparison of both apo and holo forms of the same nuclear receptor. In the crystal, the receptor is monomeric and exhibits a canonical agonist conformation without direct contacts between the ligand and the transactivation helix H12. Comparison with the unliganded RXRalpha LBD structure reveals the molecular mechanisms of ligand-induced conformational changes and allows us to describe at the atomic level how these changes generate the proper protein interface involved in nuclear receptor-coactivator interaction.