1k4w
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(New page: 200px<br /> <applet load="1k4w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1k4w, resolution 1.90Å" /> '''X-ray structure of ...)
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Revision as of 15:40, 12 November 2007
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X-ray structure of the orphan nuclear receptor ROR beta ligand-binding domain in the active conformation
Overview
The retinoic acid-related orphan receptor beta (RORbeta) exhibits a highly, restricted neuronal-specific expression pattern in brain, retina and, pineal gland. So far, neither a natural RORbeta target gene nor a, functional ligand have been identified, and the physiological role of the, receptor is not well understood. We present the crystal structure of the, ligand-binding domain (LBD) of RORbeta containing a bound stearate ligand, and complexed with a coactivator peptide. In the crystal, the monomeric, LBD adopts the canonical agonist-bound form. The fatty acid, ligand-coactivator peptide combined action stabilizes the, transcriptionally active conformation. The large ligand-binding pocket is, strictly hydrophobic on the AF-2 side and more polar on the beta-sheet, side where the carboxylate group of the ligand binds. Site-directed, mutagenesis experiments validate the significance of the present, structure. Homology modeling of the other isotypes will help to design, isotype-selective agonists and antagonists that can be used to, characterize the physiological functions of RORs. In addition, our, crystallization strategy can be extended to other orphan nuclear, receptors, providing a powerful tool to delineate their functions.
About this Structure
1K4W is a Protein complex structure of sequences from Rattus norvegicus with STE as ligand. Full crystallographic information is available from OCA.
Reference
X-ray structure of the orphan nuclear receptor RORbeta ligand-binding domain in the active conformation., Stehlin C, Wurtz JM, Steinmetz A, Greiner E, Schule R, Moras D, Renaud JP, EMBO J. 2001 Nov 1;20(21):5822-31. PMID:11689423
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