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研究揭示马钱子碱激活人类苦味受体TAS2R46的结构基础
作者:小柯机器人 发布时间:2022/9/18 20:51:29

上海科技大学华甜、刘志杰等研究人员合作揭示马钱子碱激活人类苦味受体TAS2R46的结构基础。2022年9月15日出版的《科学》杂志发表了这项成果。

研究人员报告了人类TAS2R46与嵌合微型G蛋白味导素的冷冻电镜结构,包括马钱子碱结合和apo形式。TAS2R46的几个特征被披露,包括与已知GPCR相比较的独特受体结构、一个新的"切换开关"、激活相关的模体以及与迷你G蛋白味导素的预耦合。此外,TAS2R46的动态胞外部分和更静态的胞内部分表明可能有不同的配体识别和激活过程。这项研究为进一步探索其他苦味受体及其治疗应用提供了基础。

据了解,味觉感知是一个复杂的化学感觉过程,而苦味感知是由2型味觉受体(TAS2R)或T类G蛋白偶联受体介导的。由于缺乏实验性受体结构,理解味觉背后的详细分子机制受到阻碍。

附:英文原文

Title: Structural basis for strychnine activation of human bitter taste receptor TAS2R46

Author: Weixiu Xu, Lijie Wu, Shenhui Liu, Xiao Liu, Xiaoling Cao, Cui Zhou, Jinyi Zhang, You Fu, Yu Guo, Yiran Wu, Qiwen Tan, Ling Wang, Junlin Liu, Longquan Jiang, Zhongbo Fan, Yuan Pei, Jingyi Yu, Jianjun Cheng, Suwen Zhao, Xiaojiang Hao, Zhi-Jie Liu, Tian Hua

Issue&Volume: 2022-09-16

Abstract: Taste sensing is a sophisticated chemosensory process, and bitter taste perception is mediated by type 2 taste receptors (TAS2Rs), or class T G protein–coupled receptors. Understanding the detailed molecular mechanisms behind taste sensation is hindered by a lack of experimental receptor structures. Here, we report the cryo–electron microscopy structures of human TAS2R46 complexed with chimeric mini–G protein gustducin, in both strychnine-bound and apo forms. Several features of TAS2R46 are disclosed, including distinct receptor structures that compare with known GPCRs, a new “toggle switch,” activation-related motifs, and precoupling with mini–G protein gustducin. Furthermore, the dynamic extracellular and more-static intracellular parts of TAS2R46 suggest possible diverse ligand-recognition and activation processes. This study provides a basis for further exploration of other bitter taste receptors and their therapeutic applications.

DOI: abo1633

Source: https://www.science.org/doi/10.1126/science.abo1633

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037