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TitleStructural basis for strychnine activation of human bitter taste receptor TAS2R46.
Journal, issue, pagesScience, Vol. 377, Issue 6612, Page 1298-1304, Year 2022
Publish dateSep 16, 2022
AuthorsWeixiu 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 /
PubMed AbstractTaste 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 ...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.
External linksScience / PubMed:36108005
MethodsEM (single particle)
Resolution3.01 - 3.08 Å
Structure data

33364

7xp4

EMDB-33364, PDB-7xp4:
Cryo-EM structure of a class T GPCR in apo state
Method: EM (single particle) / Resolution: 3.01 Å

33365

7xp5

EMDB-33365, PDB-7xp5:
Cryo-EM structure of a class T GPCR in ligand-free state
Method: EM (single particle) / Resolution: 3.08 Å

33366

7xp6

EMDB-33366, PDB-7xp6:
Cryo-EM structure of a class T GPCR in active state
Method: EM (single particle) / Resolution: 3.01 Å

Chemicals

ChemComp-SY9:
STRYCHNINE / alkaloid*YM / Strychnine

Source
  • homo sapiens (human)
  • acetivibrio thermocellus (bacteria)
KeywordsMEMBRANE PROTEIN / G protein-coupled receptor / taste type 2 receptors / cryo-electron microscopy structure

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