| http://purl.uniprot.org/citations/22875855 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22875855 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22875855 | http://www.w3.org/2000/01/rdf-schema#comment | "Oxysterols are oxygenated cholesterol derivates that are emerging as a physiologically important group of molecules. Although they regulate a range of cellular processes, only few oxysterol-binding effector proteins have been identified, and the knowledge of their binding mode is limited. Recently, the family of G protein-coupled seven transmembrane-spanning receptors (7TM receptors) was added to this group. Specifically, the Epstein-Barr virus-induced gene 2 (EBI2 or GPR183) was shown to be activated by several oxysterols, most potently by 7α,25-dihydroxycholesterol (7α,25-OHC). Nothing is known about the binding mode, however. Using mutational analysis, we identify here four key residues for 7α,25-OHC binding: Arg-87 in TM-II (position II:20/2.60), Tyr-112 and Tyr-116 (positions III:09/3.33 and III:13/3.37) in TM-III, and Tyr-260 in TM-VI (position VI:16/6.51). Substituting these residues with Ala and/or Phe results in a severe decrease in agonist binding and receptor activation. Docking simulations suggest that Tyr-116 interacts with the 3β-OH group in the agonist, Tyr-260 with the 7α-OH group, and Arg-87, either directly or indirectly, with the 25-OH group, although nearby residues likely also contribute. In addition, Tyr-112 is involved in 7α,25-OHC binding but via hydrophobic interactions. Finally, we show that II:20/2.60 constitutes an important residue for ligand binding in receptors carrying a positively charged residue at this position. This group is dominated by lipid- and nucleotide-activated receptors, here exemplified by the CysLTs, P2Y12, and P2Y14. In conclusion, we present the first molecular characterization of oxysterol binding to a 7TM receptor and identify position II:20/2.60 as a generally important residue for ligand binding in certain 7TM receptors."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.387894"xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.387894"xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Rosenkilde M.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Rosenkilde M.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Sailer A.W."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Sailer A.W."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Laurent S."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Laurent S."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Wolf R.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Wolf R.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Arfelt K.N."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Arfelt K.N."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Benned-Jensen T."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Benned-Jensen T."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Frimurer T."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Frimurer T."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Larsen H.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Larsen H.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Madsen C.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Madsen C.M."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Norn C."xsd:string |
| http://purl.uniprot.org/citations/22875855 | http://purl.uniprot.org/core/author | "Norn C."xsd:string |