Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli
Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli
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DOI：
10.1016/j.cub.2005.09.037
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发表时间：
2005-11-08
期刊：
影响因子：
9.2
通讯作者：
Munger, SD
中科院分区：
文献类型：
--
作者：
Nie, Y;Vigues, S;Munger, SD
动物利用数百种不同的G蛋白偶联受体（GPCR）型化学感觉受体来检测环境中的各种化学信号，包括气味、信息素和味觉物质。然而，这些受体选择性地与其同源配体相互作用的分子机制仍然知之甚少。越来越多的证据表明，许多化学感觉受体存在于多聚体复合物中[2-4]，尽管人们对单个亚基对受体功能的相对贡献知之甚少。在这里，我们报道了异质T1R2: T1R3甜味受体中的两个亚基[2,5 -10]中的每一个都结合了甜味刺激，尽管具有不同的亲和力和构象变化。此外，通过引入与行为小鼠[11]的甜味敏感性下降相关的单个氨基酸变化，T1R3的配体亲和力急剧降低。因此，单个T1R亚基增加了甜味受体的接受范围，为甜味表型变异提供了功能机制。
Animals utilize hundreds of distinct G protein-coupled receptor (GPCR)-type chemosensory receptors to detect a diverse array of chemical signals in their environment, including odors, pheromones, and tastants [1]. However, the molecular mechanisms by which these receptors selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes [2-4], though little is known about the relative contributions of individual subunits to receptor functions. Here, we report that each of the two subunits in the heteromeric T1R2: T1R3 sweet taste receptor [2, 5-10] binds sweet stimuli though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in behaving mice [11]. Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.