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Chapitre d'ouvrage

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.
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Soumis le : mardi 29 décembre 2015 - 20:16:19
Dernière modification le : mercredi 28 septembre 2022 - 15:08:48




Marie-Annick Persuy, Guenhaël Sanz, Anne Tromelin, Thierry Thomas-Danguin, Jean-Francois Gibrat, et al.. Mammalian olfactory receptors: Molecular mechanisms of odorant detection, 3D-modeling, and structure–activity relationships. Molecular basis of olfaction, 130, Chapter 1 - Molecular Basis of Olfaction, Academic Press, 131 p., 2015, Progress in Molecular Biology and Translational Science, 978-0-12-802912-1. ⟨10.1016/bs.pmbts.2014.11.001⟩. ⟨hal-01249030⟩



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