title: The mouse eugenol odorant receptor: structural and functional plasticity of a broadly tuned odorant binding pocket.
abstract: Molecular interactions of odorants with their olfactory receptors (ORs) are of central importance for the ability of the mammalian olfactory system to detect and discriminate a vast variety of odors with a limited set of receptors. How a particular OR binds and distinguishes different odorant molecules remains largely unknown on a structural basis. Here we investigated this question for the mouse eugenol receptor (mOR-EG). By screening a large odorant library, we discovered a wide range of chemical structures activating the receptor in heterologous mammalian cells. Potent agonists comprise (i) benzene, (ii) cyclohexane, or (iii) polycyclic structures substituted with alcohol, aldehyde, keto, ether, or esterified carboxylic groups. To detect those amino acids within the receptor that are in contact with a particular bound odorant molecule, we investigated how distinct mOR-EG point mutants were activated by the different odorant agonists found for the wild-type receptor. We identified 11 amino acids as a part of the receptor's ligand binding pocket. Molecular modeling predicted 10 of these residues in transmembrane helices TM3-TM6 and one in the extracellular loop between TM2 and TM3. These amino acids participate in odorant binding with variable importance depending on the type of odorant, revealing functional "fingerprints" of ligand-receptor interactions.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Baud
authors.forename: Sylvain
authors.initials: S
authors.lastname: Etter
authors.forename: Morena
authors.initials: M
authors.lastname: Spreafico
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bordoli
authors.forename: Torsten
authors.initials: T
authors.lastname: Schwede
authors.forename: Horst
authors.initials: H
authors.lastname: Vogel
authors.forename: Horst
authors.initials: H
authors.lastname: Pick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005054:Eugenol / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D018035:Receptors, Odorant / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; D018035:Receptors, Odorant; D005054:Eugenol