1FBY

CRYSTAL STRUCTURE OF THE HUMAN RXR ALPHA LIGAND BINDING DOMAIN BOUND TO 9-CIS RETINOIC ACID

Summary for 1FBY

• Entry DOI: 10.2210/pdb1fby/pdb
• Descriptor: RETINOIC ACID RECEPTOR RXR-ALPHA, (9cis)-retinoic acid (3 entities in total)
• Functional Keywords: nuclear receptor, protein-ligand complex, retinoid receptor, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P19793
• Total number of polymer chains: 2
• Total formula weight: 54110.75

Authors

Egea, P.F.,Mitschler, A.,Rochel, N.,Ruff, M.,Chambon, P.,Moras, D. (deposition date: 2000-07-17, release date: 2000-07-28, Last modification date: 2024-02-07)

Primary citation

Egea, P.F.,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., 19:2592-2601, 2000

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.

PubMed: 10835357
DOI: 10.1093/emboj/19.11.2592

Experimental method

X-RAY DIFFRACTION (2.25 Å)