title: Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism.
abstract: Mammals detect and discriminate numerous odors via a large family of G protein-coupled odorant receptors (ORs). However, little is known about the molecular and structural basis underlying OR response properties. Using site-directed mutagenesis and computational modeling, we studied ORs sharing high sequence homology but with different response properties. When tested in heterologous cells by diverse odorants, MOR256-3 responded broadly to many odorants, whereas MOR256-8 responded weakly to a few odorants. Out of 36 mutant MOR256-3 ORs, the majority altered the responses to different odorants in a similar manner and the overall response of an OR was positively correlated with its basal activity, an indication of ligand-independent receptor activation. Strikingly, a single mutation in MOR256-8 was sufficient to confer both high basal activity and broad responsiveness to this receptor. These results suggest that broad responsiveness of an OR is at least partially attributed to its activation likelihood.
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Chemistry Nice, UMR 7272, University Nice Sophia Antipolis, Centre National de la Recherche Scientifique, 06108 Nice Cedex 2, France;
authors.forename: Claire A
authors.initials: CA
authors.lastname: de March
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Mengjue J
authors.initials: MJ
authors.lastname: Ni
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Kaylin A
authors.initials: KA
authors.lastname: Adipietro
authors.affiliation: Institute of Chemistry Nice, UMR 7272, University Nice Sophia Antipolis, Centre National de la Recherche Scientifique, 06108 Nice Cedex 2, France; minghong@mail.med.upenn.edu matsu004@mc.duke.edu jerome.golebiowski@unice.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Golebiowski
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710; Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710 minghong@mail.med.upenn.edu matsu004@mc.duke.edu jerome.golebiowski@unice.fr.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsunami
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; minghong@mail.med.upenn.edu matsu004@mc.duke.edu jerome.golebiowski@unice.fr.
authors.forename: Minghong
authors.initials: M
authors.lastname: Ma
mesh_terms: D000818:Animals; D002460:Cell Line; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*
chemical_list: D018035:Receptors, Odorant
keywords: G protein-coupled receptor; broad responsiveness; computational modeling; odorant receptor; site-directed mutagenesis