The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding

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 mol...

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Autores principales: Shim, Tammy, Pacalon, Jody, Kim, Won-Cheol, Cong, Xiaojing, Topin, Jérémie, Golebiowski, Jérôme, Moon, Cheil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604345/
https://www.ncbi.nlm.nih.gov/pubmed/36293357
http://dx.doi.org/10.3390/ijms232012501
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author Shim, Tammy
Pacalon, Jody
Kim, Won-Cheol
Cong, Xiaojing
Topin, Jérémie
Golebiowski, Jérôme
Moon, Cheil
author_facet Shim, Tammy
Pacalon, Jody
Kim, Won-Cheol
Cong, Xiaojing
Topin, Jérémie
Golebiowski, Jérôme
Moon, Cheil
author_sort Shim, Tammy
collection PubMed
description 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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spelling pubmed-96043452022-10-27 The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding Shim, Tammy Pacalon, Jody Kim, Won-Cheol Cong, Xiaojing Topin, Jérémie Golebiowski, Jérôme Moon, Cheil Int J Mol Sci Article 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. MDPI 2022-10-18 /pmc/articles/PMC9604345/ /pubmed/36293357 http://dx.doi.org/10.3390/ijms232012501 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shim, Tammy
Pacalon, Jody
Kim, Won-Cheol
Cong, Xiaojing
Topin, Jérémie
Golebiowski, Jérôme
Moon, Cheil
The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
title The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
title_full The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
title_fullStr The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
title_full_unstemmed The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
title_short The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
title_sort third extracellular loop of mammalian odorant receptors is involved in ligand binding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604345/
https://www.ncbi.nlm.nih.gov/pubmed/36293357
http://dx.doi.org/10.3390/ijms232012501
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