1n4h
From Proteopedia
(New page: 200px<br /> <applet load="1n4h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n4h, resolution 2.1Å" /> '''Characterization of ...) |
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| - | [[Image:1n4h.gif|left|200px]]<br /> | + | [[Image:1n4h.gif|left|200px]]<br /><applet load="1n4h" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1n4h" size=" | + | |
caption="1n4h, resolution 2.1Å" /> | caption="1n4h, resolution 2.1Å" /> | ||
'''Characterization of ligands for the orphan nuclear receptor RORbeta'''<br /> | '''Characterization of ligands for the orphan nuclear receptor RORbeta'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Retinoids regulate gene expression through binding to the nuclear retinoic | + | Retinoids regulate gene expression through binding to the nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In contrast, no ligands for the retinoic acid receptor-related orphan receptors beta and gamma (ROR beta and gamma) have been identified, yet structural data and structure-function analyses indicate that ROR beta is a ligand-regulated nuclear receptor. Using nondenaturing mass spectrometry and scintillation proximity assays we found that all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta ligand-binding domain (LBD). The crystal structures of the complex with ATRA and with the synthetic analog ALRT 1550 reveal the binding modes of these ligands. ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity suggesting that high-affinity, subtype-specific ligands could be designed for the identification of ROR beta target genes. Our results identify ROR beta as a retinoid-regulated nuclear receptor, providing a novel pathway for retinoid action. |
==About this Structure== | ==About this Structure== | ||
| - | 1N4H 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 REA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1N4H 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=REA:'>REA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N4H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Dorsselaer, A | + | [[Category: Dorsselaer, A Van.]] |
[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
| - | [[Category: Renaud, J | + | [[Category: Renaud, J P.]] |
[[Category: Sanglier, S.]] | [[Category: Sanglier, S.]] | ||
[[Category: Schuele, R.]] | [[Category: Schuele, R.]] | ||
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[[Category: protein-peptide-ligand complex]] | [[Category: protein-peptide-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:08 2008'' |
Revision as of 12:02, 21 February 2008
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Characterization of ligands for the orphan nuclear receptor RORbeta
Overview
Retinoids regulate gene expression through binding to the nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In contrast, no ligands for the retinoic acid receptor-related orphan receptors beta and gamma (ROR beta and gamma) have been identified, yet structural data and structure-function analyses indicate that ROR beta is a ligand-regulated nuclear receptor. Using nondenaturing mass spectrometry and scintillation proximity assays we found that all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta ligand-binding domain (LBD). The crystal structures of the complex with ATRA and with the synthetic analog ALRT 1550 reveal the binding modes of these ligands. ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity suggesting that high-affinity, subtype-specific ligands could be designed for the identification of ROR beta target genes. Our results identify ROR beta as a retinoid-regulated nuclear receptor, providing a novel pathway for retinoid action.
About this Structure
1N4H is a Protein complex structure of sequences from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta., Stehlin-Gaon C, Willmann D, Zeyer D, Sanglier S, Van Dorsselaer A, Renaud JP, Moras D, Schule R, Nat Struct Biol. 2003 Oct;10(10):820-5. Epub 2003 Sep 7. PMID:12958591
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