The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket

Abstract Although bitter taste receptors (TAS2Rs) are important for human health, little is known of the determinants of ligand specificity. TAS2Rs such as TAS2R16 help define gustatory perception and dietary preferences that ultimately influence human health and disease. Each TAS2R must accommodate...

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Autores principales:	Anu Thomas, Chidananda Sulli, Edgar Davidson, Eli Berdougo, Morganne Phillips, Bridget A. Puffer, Cheryl Paes, Benjamin J. Doranz, Joseph B. Rucker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12f45ce1b6b94a4e81f404c14a6ac2b5
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spelling	oai:doaj.org-article:12f45ce1b6b94a4e81f404c14a6ac2b52021-12-02T15:06:27ZThe Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket10.1038/s41598-017-07256-y2045-2322https://doaj.org/article/12f45ce1b6b94a4e81f404c14a6ac2b52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07256-yhttps://doaj.org/toc/2045-2322Abstract Although bitter taste receptors (TAS2Rs) are important for human health, little is known of the determinants of ligand specificity. TAS2Rs such as TAS2R16 help define gustatory perception and dietary preferences that ultimately influence human health and disease. Each TAS2R must accommodate a broad diversity of chemical structures while simultaneously achieving high specificity so that diverse bitter toxins can be detected without all foods tasting bitter. However, how these G protein-coupled receptors achieve this balance is poorly understood. Here we used a comprehensive mutation library of human TAS2R16 to map its interactions with existing and novel agonists. We identified 13 TAS2R16 residues that contribute to ligand specificity and 38 residues whose mutation eliminated signal transduction by all ligands, providing a comprehensive assessment of how this GPCR binds and signals. Our data suggest a model in which hydrophobic residues on TM3 and TM7 form a broad ligand-binding pocket that can accommodate the diverse structural features of β-glycoside ligands while still achieving high specificity.Anu ThomasChidananda SulliEdgar DavidsonEli BerdougoMorganne PhillipsBridget A. PufferCheryl PaesBenjamin J. DoranzJoseph B. RuckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anu Thomas Chidananda Sulli Edgar Davidson Eli Berdougo Morganne Phillips Bridget A. Puffer Cheryl Paes Benjamin J. Doranz Joseph B. Rucker The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
description	Abstract Although bitter taste receptors (TAS2Rs) are important for human health, little is known of the determinants of ligand specificity. TAS2Rs such as TAS2R16 help define gustatory perception and dietary preferences that ultimately influence human health and disease. Each TAS2R must accommodate a broad diversity of chemical structures while simultaneously achieving high specificity so that diverse bitter toxins can be detected without all foods tasting bitter. However, how these G protein-coupled receptors achieve this balance is poorly understood. Here we used a comprehensive mutation library of human TAS2R16 to map its interactions with existing and novel agonists. We identified 13 TAS2R16 residues that contribute to ligand specificity and 38 residues whose mutation eliminated signal transduction by all ligands, providing a comprehensive assessment of how this GPCR binds and signals. Our data suggest a model in which hydrophobic residues on TM3 and TM7 form a broad ligand-binding pocket that can accommodate the diverse structural features of β-glycoside ligands while still achieving high specificity.
format	article
author	Anu Thomas Chidananda Sulli Edgar Davidson Eli Berdougo Morganne Phillips Bridget A. Puffer Cheryl Paes Benjamin J. Doranz Joseph B. Rucker
author_facet	Anu Thomas Chidananda Sulli Edgar Davidson Eli Berdougo Morganne Phillips Bridget A. Puffer Cheryl Paes Benjamin J. Doranz Joseph B. Rucker
author_sort	Anu Thomas
title	The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
title_short	The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
title_full	The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
title_fullStr	The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
title_full_unstemmed	The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
title_sort	bitter taste receptor tas2r16 achieves high specificity and accommodates diverse glycoside ligands by using a two-faced binding pocket
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/12f45ce1b6b94a4e81f404c14a6ac2b5
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The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket

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