Structural basis for strychnine activation of human bitter taste receptor TAS2R46.

Science (New York, N.Y.) 2022 Sep 16

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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.

Citation

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. Structural basis for strychnine activation of human bitter taste receptor TAS2R46. Science (New York, N.Y.). 2022 Sep 16;377(6612):1298-1304