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1uhl

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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'''
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===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.
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{{ABSTRACT_PUBMED_12970175}}
==About this Structure==
==About this Structure==
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[[Category: Zachrisson, K.]]
[[Category: Zachrisson, K.]]
[[Category: Ligand-binding domain]]
[[Category: Ligand-binding domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:14:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:20:03 2008''

Revision as of 11:20, 29 July 2008

Image:1uhl.png

Template:STRUCTURE 1uhl

Crystal structure of the LXRalfa-RXRbeta LBD heterodimer

Template:ABSTRACT PUBMED 12970175

About this Structure

1UHL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation., Svensson S, Ostberg T, Jacobsson M, Norstrom C, Stefansson K, Hallen D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L, EMBO J. 2003 Sep 15;22(18):4625-33. PMID:12970175

Page seeded by OCA on Tue Jul 29 14:20:03 2008

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