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| [[Image:1uhl.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1uhl| PDB=1uhl | SCENE= }} | | {{STRUCTURE_1uhl| PDB=1uhl | SCENE= }} |
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| '''Crystal structure of the LXRalfa-RXRbeta LBD heterodimer'''
| | ===Crystal structure of the LXRalfa-RXRbeta LBD heterodimer=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_12970175}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12970175 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12970175}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Zachrisson, K.]] | | [[Category: Zachrisson, K.]] |
| [[Category: Ligand-binding domain]] | | [[Category: Ligand-binding domain]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:14:27 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:20:03 2008'' |
