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1k4w
From Proteopedia
(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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| - | [[Image:1k4w.gif|left|200px]]<br /> | + | [[Image:1k4w.gif|left|200px]]<br /><applet load="1k4w" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1k4w" size=" | + | |
caption="1k4w, resolution 1.90Å" /> | caption="1k4w, resolution 1.90Å" /> | ||
'''X-ray structure of the orphan nuclear receptor ROR beta ligand-binding domain in the active conformation'''<br /> | '''X-ray structure of the orphan nuclear receptor ROR beta ligand-binding domain in the active conformation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The retinoic acid-related orphan receptor beta (RORbeta) exhibits a highly | + | 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== | ==About this Structure== | ||
| - | 1K4W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with STE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1K4W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=STE:'>STE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4W OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Greiner, E.]] | [[Category: Greiner, E.]] | ||
[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
| - | [[Category: Renaud, J | + | [[Category: Renaud, J P.]] |
[[Category: Schuele, R.]] | [[Category: Schuele, R.]] | ||
[[Category: Stehlin, C.]] | [[Category: Stehlin, C.]] | ||
[[Category: Steinmetz, A.]] | [[Category: Steinmetz, A.]] | ||
| - | [[Category: Wurtz, J | + | [[Category: Wurtz, J M.]] |
[[Category: STE]] | [[Category: STE]] | ||
[[Category: alpha-helical sandwich]] | [[Category: alpha-helical sandwich]] | ||
| Line 26: | Line 25: | ||
[[Category: transcriptionally active conformation]] | [[Category: transcriptionally active conformation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:30:10 2008'' |
Revision as of 11:30, 21 February 2008
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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 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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