Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection

Umami and sweet taste detection is mediated by the activation of the TAS1R1/TAS1R3 and TAS1R2/TAS1R3 receptors, respectively. TAS1R2-Venus flytrap domain (VFT) constitutes the primary ligand-binding site for most of the sweeteners whereas TAS1R1-VFT contains the orthosteric binding site for umami co...

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Main Authors: Christine Belloir, Lucie Moitrier, Adeline Karolkowski, Nicolas Poirier, Fabrice Neiers, Loïc Briand
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Food Chemistry: Molecular Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666566225000073
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author Christine Belloir
Lucie Moitrier
Adeline Karolkowski
Nicolas Poirier
Fabrice Neiers
Loïc Briand
author_facet Christine Belloir
Lucie Moitrier
Adeline Karolkowski
Nicolas Poirier
Fabrice Neiers
Loïc Briand
author_sort Christine Belloir
collection DOAJ
description Umami and sweet taste detection is mediated by the activation of the TAS1R1/TAS1R3 and TAS1R2/TAS1R3 receptors, respectively. TAS1R2-Venus flytrap domain (VFT) constitutes the primary ligand-binding site for most of the sweeteners whereas TAS1R1-VFT contains the orthosteric binding site for umami compounds. Inosine-5′-monophosphate (IMP), previously known to potentiate umami taste, binds to a site of TAS1R1-VFT adjacent to the L-glutamate site leading to umami synergy. However, the involvement of the TAS1R3 subunit in umami receptor-ligand interactions or in synergy with IMP has never been demonstrated. To elucidate the VFT contribution to umami and sweet detection, we expressed human TAS1R1- and TAS1R3-VFTs in bacteria. Ligand binding studies quantified by intrinsic tryptophan fluorescence revealed that both TAS1R1- and TAS1R3-VFTs are able to interact with umami compounds. Cellular assays revealed that IMP is able, like cyclamate, to modulate the response of TAS1R2/TAS1R3 and TAS1R3 alone stimulated by calcium ions. IMP also acted as an enhancer of TAS1R2/TAS1R3 when stimulated with sucralose, neotame and cyclamate. Taking together, our data demonstrated that IMP modulates sweet compound detection at the receptor level acting via the TAS1R3 subunit. This research suggests more complex receptor interactions between umami and sweet taste qualities and paves the way for development of new sweetness enhancers.
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spelling doaj-art-d1fbde1c2762401cbac133a91fc1ea162025-08-20T03:45:28ZengElsevierFood Chemistry: Molecular Sciences2666-56622025-06-011010024610.1016/j.fochms.2025.100246Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detectionChristine Belloir0Lucie Moitrier1Adeline Karolkowski2Nicolas Poirier3Fabrice Neiers4Loïc Briand5Corresponding authors.; Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe, F-21000 Dijon, FranceCentre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe, F-21000 Dijon, FranceCentre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe, F-21000 Dijon, FranceCentre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe, F-21000 Dijon, FranceCentre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe, F-21000 Dijon, FranceCorresponding authors.; Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe, F-21000 Dijon, FranceUmami and sweet taste detection is mediated by the activation of the TAS1R1/TAS1R3 and TAS1R2/TAS1R3 receptors, respectively. TAS1R2-Venus flytrap domain (VFT) constitutes the primary ligand-binding site for most of the sweeteners whereas TAS1R1-VFT contains the orthosteric binding site for umami compounds. Inosine-5′-monophosphate (IMP), previously known to potentiate umami taste, binds to a site of TAS1R1-VFT adjacent to the L-glutamate site leading to umami synergy. However, the involvement of the TAS1R3 subunit in umami receptor-ligand interactions or in synergy with IMP has never been demonstrated. To elucidate the VFT contribution to umami and sweet detection, we expressed human TAS1R1- and TAS1R3-VFTs in bacteria. Ligand binding studies quantified by intrinsic tryptophan fluorescence revealed that both TAS1R1- and TAS1R3-VFTs are able to interact with umami compounds. Cellular assays revealed that IMP is able, like cyclamate, to modulate the response of TAS1R2/TAS1R3 and TAS1R3 alone stimulated by calcium ions. IMP also acted as an enhancer of TAS1R2/TAS1R3 when stimulated with sucralose, neotame and cyclamate. Taking together, our data demonstrated that IMP modulates sweet compound detection at the receptor level acting via the TAS1R3 subunit. This research suggests more complex receptor interactions between umami and sweet taste qualities and paves the way for development of new sweetness enhancers.http://www.sciencedirect.com/science/article/pii/S2666566225000073G-protein-coupled receptorTaste receptorSweetenerUmamiRibonucleotide
spellingShingle Christine Belloir
Lucie Moitrier
Adeline Karolkowski
Nicolas Poirier
Fabrice Neiers
Loïc Briand
Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection
Food Chemistry: Molecular Sciences
G-protein-coupled receptor
Taste receptor
Sweetener
Umami
Ribonucleotide
title Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection
title_full Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection
title_fullStr Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection
title_full_unstemmed Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection
title_short Inosine-5′-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection
title_sort inosine 5 monophosphate interacts with the tas1r3 subunit to enhance sweet taste detection
topic G-protein-coupled receptor
Taste receptor
Sweetener
Umami
Ribonucleotide
url http://www.sciencedirect.com/science/article/pii/S2666566225000073
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