title: Mammalian olfactory receptors: molecular mechanisms of odorant detection, 3D-modeling, and structure-activity relationships.
abstract: This chapter describes the main characteristics of olfactory receptor (OR) genes of vertebrates, including generation of this large multigenic family and pseudogenization. OR genes are compared in relation to evolution and among species. OR gene structure and selection of a given gene for expression in an olfactory sensory neuron (OSN) are tackled. The specificities of OR proteins, their expression, and their function are presented. The expression of OR proteins in locations other than the nasal cavity is regulated by different mechanisms, and ORs display various additional functions. A conventional olfactory signal transduction cascade is observed in OSNs, but individual ORs can also mediate different signaling pathways, through the involvement of other molecular partners and depending on the odorant ligand encountered. ORs are engaged in constitutive dimers. Ligand binding induces conformational changes in the ORs that regulate their level of activity depending on odorant dose. When present, odorant binding proteins induce an allosteric modulation of OR activity. Since no 3D structure of an OR has been yet resolved, modeling has to be performed using the closest G-protein-coupled receptor 3D structures available, to facilitate virtual ligand screening using the models. The study of odorant binding modes and affinities may infer best-bet OR ligands, to be subsequently checked experimentally. The relationship between spatial and steric features of odorants and their activity in terms of perceived odor quality are also fields of research that development of computing tools may enhance.
authors.affiliation: INRA UR 1197 NeuroBiologie de l'Olfaction, Domaine de Vilvert, Jouy-en-Josas, France.
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Persuy
authors.affiliation: INRA UR 1197 NeuroBiologie de l'Olfaction, Domaine de Vilvert, Jouy-en-Josas, France.
authors.forename: Guenhaël
authors.initials: G
authors.lastname: Sanz
authors.affiliation: INRA UMR 1129 Flaveur, Vision et Comportement du Consommateur, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tromelin
authors.affiliation: INRA UMR 1129 Flaveur, Vision et Comportement du Consommateur, Dijon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Thomas-Danguin
authors.affiliation: INRA UR1077 Mathématique Informatique et Génome, Domaine de Vilvert, Jouy-en-Josas, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gibrat
authors.affiliation: INRA UR 1197 NeuroBiologie de l'Olfaction, Domaine de Vilvert, Jouy-en-Josas, France. Electronic address: edith.pajot@jouy.inra.fr.
authors.forename: Edith
authors.initials: E
authors.lastname: Pajot-Augy
mesh_terms: D000818:Animals; D006801:Humans; D021621:Imaging, Three-Dimensional; D009812:Odorants / Q000032:analysis*; D009831:Olfactory Mucosa / Q000502:physiology*; D018035:Receptors, Odorant / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D018035:Receptors, Odorant
keywords: 3D-QSAR modeling; 3D-modeling; Allosteric modulation; Dimerization; Mammals; Odorant binding proteins; Odorant ligands; Olfactory receptor proteins; Screening