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Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in o...

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Autores principales: Biarnés, Xevi, Marchiori, Alessandro, Giorgetti, Alejandro, Lanzara, Carmela, Gasparini, Paolo, Carloni, Paolo, Born, Stephan, Brockhoff, Anne, Behrens, Maik, Meyerhof, Wolfgang
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928277/
https://www.ncbi.nlm.nih.gov/pubmed/20811630
http://dx.doi.org/10.1371/journal.pone.0012394
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author Biarnés, Xevi
Marchiori, Alessandro
Giorgetti, Alejandro
Lanzara, Carmela
Gasparini, Paolo
Carloni, Paolo
Born, Stephan
Brockhoff, Anne
Behrens, Maik
Meyerhof, Wolfgang
author_facet Biarnés, Xevi
Marchiori, Alessandro
Giorgetti, Alejandro
Lanzara, Carmela
Gasparini, Paolo
Carloni, Paolo
Born, Stephan
Brockhoff, Anne
Behrens, Maik
Meyerhof, Wolfgang
author_sort Biarnés, Xevi
collection PubMed
description Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models.
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spelling pubmed-29282772010-09-01 Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor Biarnés, Xevi Marchiori, Alessandro Giorgetti, Alejandro Lanzara, Carmela Gasparini, Paolo Carloni, Paolo Born, Stephan Brockhoff, Anne Behrens, Maik Meyerhof, Wolfgang PLoS One Research Article Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models. Public Library of Science 2010-08-25 /pmc/articles/PMC2928277/ /pubmed/20811630 http://dx.doi.org/10.1371/journal.pone.0012394 Text en Biarnés et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Biarnés, Xevi
Marchiori, Alessandro
Giorgetti, Alejandro
Lanzara, Carmela
Gasparini, Paolo
Carloni, Paolo
Born, Stephan
Brockhoff, Anne
Behrens, Maik
Meyerhof, Wolfgang
Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor
title Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor
title_full Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor
title_fullStr Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor
title_full_unstemmed Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor
title_short Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor
title_sort insights into the binding of phenyltiocarbamide (ptc) agonist to its target human tas2r38 bitter receptor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928277/
https://www.ncbi.nlm.nih.gov/pubmed/20811630
http://dx.doi.org/10.1371/journal.pone.0012394
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