Dynamic Interaction Mechanisms of Taste Receptors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09818
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Sanematsu Keisuke 九州大学, 歯学研究院, 講師 (70567502)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 味覚受容体 / 甘味 / 動的活性化機構

Outline of Final Research Achievements

The molecular mechanisms of dynamic receptor activation and inactivation that occur after the binding of taste molecules to their receptors have remained unknown because the analysis of the interaction between taste substances and taste receptors has focused on the static binding form. In this study, by introducing molecular dynamics simulations, we succeeded in reproducing the species-specific sensitivity of the sweet inhibitors gymnemic acid and lactisole and the artificial sweetener cyclamate in the transmembrane domain of the sweet taste receptor subunit TAS1R3. In particular, cyclamate was found to act as an artificial sweetener in the human receptor and as an inhibitor in the mouse receptor.

Free Research Field

味覚

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、味覚受容体の種特異的な感受性をシミュレーション上で再現可能であることを示した。これらは、甘味受容体の活性化・不活性化メカニズムの理解を深めるだけでなく、全身に発現する甘味受容体の制御機構の理解に重要であり、新規味覚修飾物質や機能性食品の開発や創薬に繋がる。また他のクラスC Gタンパク質共役型受容体の活性化機構に重要な知見を与える。