The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding |
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Authors: | Tammy Shim,Jody Pacalon,Won-Cheol Kim,Xiaojing Cong,Jé ré mie Topin,Jé rô me Golebiowski,Cheil Moon |
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Affiliation: | 1.Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Korea;2.Institut de Chimie de Nice UMR7272, Université Côte d’Azur, CNRS, 06108 Nice, France;3.Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, CEDEX 05, 34094 Montpellier, France |
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Abstract: | Mammals recognize chemicals in the air via G protein-coupled odorant receptors (ORs). In addition to their orthosteric binding site, other segments of these receptors modulate ligand recognition. Focusing on human hOR1A1, which is considered prototypical of class II ORs, we used a combination of molecular modeling, site-directed mutagenesis, and in vitro functional assays. We showed that the third extracellular loop of ORs (ECL3) contributes to ligand recognition and receptor activation. Indeed, site-directed mutations in ECL3 showed differential effects on the potency and efficacy of both carvones, citronellol, and 2-nonanone. |
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Keywords: | odorant receptors ECL3 ligand selectivity molecular modeling functional assays |
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