1uhl
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1uhl.gif|left|200px]] | [[Image:1uhl.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1uhl", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1uhl| PDB=1uhl | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal structure of the LXRalfa-RXRbeta LBD heterodimer''' | '''Crystal structure of the LXRalfa-RXRbeta LBD heterodimer''' | ||
| Line 35: | Line 32: | ||
[[Category: Svensson, S.]] | [[Category: Svensson, S.]] | ||
[[Category: Zachrisson, K.]] | [[Category: Zachrisson, K.]] | ||
| - | [[Category: | + | [[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 | + | |
Revision as of 08:14, 3 May 2008
Crystal structure of the LXRalfa-RXRbeta LBD heterodimer
Overview
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.
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 Sat May 3 11:14:27 2008
