The Heptahelical Domain of the Sweet Taste Receptor T1R2 Is a New Allosteric Binding Site for the Sweet Taste Modulator Amiloride That Modulates Sweet Taste in a Species-Dependent Manner
The Heptahelical Domain of the Sweet Taste Receptor T1R2 Is a New Allosteric Binding Site for the Sweet Taste Modulator Amiloride That Modulates Sweet Taste in a Species-Dependent Manner
复制标题
DOI：
10.1007/s12031-018-1156-5
复制
发表时间：
2018-10-01
影响因子：
3.1
通讯作者：
Liu, Bo
中科院分区：
文献类型：
--
作者：
Zhao, Meng;Xu, Xiang-Qun;Liu, Bo
甜味受体(异二聚体T1R2和T1R3)的活性可受甜味调节剂的调节。该复方阿米洛利可抑制人类甜味感受器的甜味敏感性。本研究描述了这种甜味抑制剂对甜味受体反应的物种依赖性调节。阿米洛利抑制人类和小鼠的甜味反应，但不能抑制松鼠猴子的甜味反应。利用人/松鼠、猴子/小鼠嵌合的T1R2和T1R3受体以及激动剂perillartin(可以激活T1R2的单一七螺旋结构域)，我们发现T1R2的七螺旋结构域是介导对这种甜味调节剂的物种依赖敏感性的分子决定因素。与甜味抑制剂乳酸(作用于T1R3)相比，阿米洛利在甜味受体上具有不同的变构结合部位，这为设计作用于T1R2的新型甜味调节剂提供了重要的新信息。
The activity of sweet taste receptor (heterodimeric T1R2 and T1R3) can be modulated by sweet regulators. The compound amiloride can inhibit the sweet sensitivity of the human sweet taste receptor. This study describes the species-dependent regulation of the response of sweet taste receptors by this sweet inhibitor. Amiloride inhibited the sweet taste response of humans and mice but not that of squirrel monkeys. Using human/squirrel monkey/mouse chimeric T1R2 and T1R3 receptors as well as the agonist perillartine (which can activate the single heptahelical domain of T1R2), we found that the heptahelical domain of T1R2 is the molecular determinant that mediates the species-dependent sensitivity to this sweet regulator. Compared to the sweet inhibitor lactisole (which acts on T1R3), amiloride has a different allosteric binding site on the sweet receptor, which is important new information for the design of novel sweet taste modulators that act on T1R2.