College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, PR China.
Food Funct. 2019 Mar 20;10(3):1280-1287. doi: 10.1039/c8fo02522c.
The aim of this study was to determine the interaction between the human umami receptor hT1R1 and a ligand while avoiding the cross-talk among various signal pathways in cells. The hT1R1 was modified and mounted onto a signal amplification system on a glassy carbon electrode surface, and the response current towards four umami ligands (sodium glutamate (MSG), disodium inosinate (IMP), disodium guanylate (GMP), and disodium succinate (SUC)) was measured. The allosteric constants of the receptor-ligand interaction were calculated by the method of sensing kinetics, and the results indicated that the sensing ability of hT1R1 towards the abovementioned four ligands was as follows: GMP > MSG > IMP > SUC. After the analysis of the molecular structure and simulation through the molecular docking model, we have found that hT1R1 is essentially a recognition receptor for the nitrogen signal in the body, and it may recognize the umami substance through its amino group. The new research method developed in this study shows promising application in the mechanism study of signal transduction and drug screening.
本研究旨在确定人鲜味受体 hT1R1 与配体之间的相互作用,同时避免细胞内各种信号通路的串扰。hT1R1 经过修饰并安装在玻璃碳电极表面的信号放大系统上,测量了对四种鲜味配体(谷氨酸钠(MSG)、肌苷酸钠(IMP)、鸟苷酸钠(GMP)和琥珀酸钠(SUC))的响应电流。通过传感动力学方法计算了受体-配体相互作用的变构常数,结果表明 hT1R1 对上述四种配体的传感能力如下:GMP>MSG>IMP>SUC。通过分子对接模型的结构分析和模拟,我们发现 hT1R1 本质上是体内氮信号的识别受体,它可能通过其氨基识别鲜味物质。本研究中开发的新研究方法在信号转导机制研究和药物筛选方面具有广阔的应用前景。