1s0x
From Proteopedia
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|PDB= 1s0x |SIZE=350|CAPTION= <scene name='initialview01'>1s0x</scene>, resolution 2.20Å | |PDB= 1s0x |SIZE=350|CAPTION= <scene name='initialview01'>1s0x</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=C3S:CHOLEST-5-EN-3-YL HYDROGEN SULFATE'>C3S</scene> | + | |LIGAND= <scene name='pdbligand=C3S:CHOLEST-5-EN-3-YL+HYDROGEN+SULFATE'>C3S</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= RORA, NR1F1, RZRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= RORA, NR1F1, RZRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s0x OCA], [http://www.ebi.ac.uk/pdbsum/1s0x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s0x RCSB]</span> | ||
}} | }} | ||
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[[Category: Kallen, J.]] | [[Category: Kallen, J.]] | ||
[[Category: Schlaeppi, J M.]] | [[Category: Schlaeppi, J M.]] | ||
| - | [[Category: C3S]] | ||
[[Category: ligand binding domain]] | [[Category: ligand binding domain]] | ||
[[Category: nuclear hormone receptor]] | [[Category: nuclear hormone receptor]] | ||
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[[Category: three-layered alpha helical sandwich]] | [[Category: three-layered alpha helical sandwich]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:35:47 2008'' |
Revision as of 20:35, 30 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | RORA, NR1F1, RZRA (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the human RORalpha ligand binding domain in complex with cholesterol sulfate at 2.2A
Overview
The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of the subfamily 1 of nuclear hormone receptors. Our recent structural and functional studies have led to the hypothesis that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. We have now solved the x-ray crystal structure of the ligand binding domain of RORalpha in complex with cholesterol-3-O-sulfate following a ligand exchange experiment. In contrast to the 3-hydroxyl of cholesterol, the 3-O-sulfate group makes additional direct hydrogen bonds with three residues of the RORalpha ligand binding domain, namely NH-Gln(289), NH-Tyr(290), and NH1-Arg(370). When compared with the complex with cholesterol, seven well ordered water molecules have been displaced, and the ligand is slightly shifted toward the hydrophilic part of the ligand binding pocket, which is ideally suited for interactions with a sulfate group. These additional ligand-protein interactions result in an increased affinity of cholesterol sulfate when compared with cholesterol, as shown by mass spectrometry analysis done under native conditions and differential scanning calorimetry. Moreover, mutational studies show that the higher binding affinity of cholesterol sulfate translates into an increased transcriptional activity of RORalpha. Our findings suggest that cholesterol sulfate could play a crucial role in the regulation of RORalpha in vivo.
About this Structure
1S0X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A., Kallen J, Schlaeppi JM, Bitsch F, Delhon I, Fournier B, J Biol Chem. 2004 Apr 2;279(14):14033-8. Epub 2004 Jan 13. PMID:14722075
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