1UHL

Crystal structure of the LXRalfa-RXRbeta LBD heterodimer

Summary for 1UHL

• Entry DOI: 10.2210/pdb1uhl/pdb
• Descriptor: Retinoic acid receptor RXR-beta, Oxysterols receptor LXR-alpha, 10-mer peptide from Nuclear receptor coactivator 2, ... (6 entities in total)
• Functional Keywords: ligand-binding domain, dna binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P28702 Q13133 Q15596
• Total number of polymer chains: 4
• Total formula weight: 57619.23

Authors

Svensson, S.,Ostberg, T.,Jacobsson, M.,Norstrom, C.,Stefansson, K.,Hallen, D.,Johansson, I.C.,Zachrisson, K.,Ogg, D.,Jendeberg, L. (deposition date: 2003-07-03, release date: 2004-06-01, Last modification date: 2023-10-25)

Primary citation

Svensson, S.,Ostberg, T.,Jacobsson, M.,Norstrom, C.,Stefansson, K.,Hallen, D.,Johansson, I.C.,Zachrisson, K.,Ogg, D.,Jendeberg, L.
Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation
Embo J., 22:4625-4633, 2003

PubMed Abstract: The nuclear receptor heterodimers of liver X receptor (LXR) and retinoid X receptor (RXR) are key transcriptional regulators of genes involved in lipid homeostasis and inflammation. We report the crystal structure of the ligand-binding domains (LBDs) of LXRalpha and RXRbeta complexed to the synthetic LXR agonist T-0901317 and the RXR agonist methoprene acid (Protein Data Base entry 1UHL). Both LBDs are in agonist conformation with GRIP-1 peptides bound at the coactivator binding sites. T-0901317 occupies the center of the LXR ligand-binding pocket and its hydroxyl head group interacts with H421 and W443, residues identified by mutational analysis as critical for ligand-induced transcriptional activation by T-0901317 and various endogenous oxysterols. The topography of the pocket suggests a common anchoring of these oxysterols via their 22-, 24- or 27-hydroxyl group to H421 and W443. Polyunsaturated fatty acids act as LXR antagonists and an E267A mutation was found to enhance their transcriptional inhibition. The present structure provides a powerful tool for the design of novel modulators that can be used to characterize further the physiological functions of the LXR-RXR heterodimer.

PubMed: 12970175
DOI: 10.1093/emboj/cdg456

Experimental method

X-RAY DIFFRACTION (2.9 Å)