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

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Title: Structural basis for strychnine activation of human bitter taste receptor TAS2R46.
Authors: Xu, Weixiu, Wu, Lijie, Liu, Shenhui, Liu, Xiao, Cao, Xiaoling, Zhou, Cui, Zhang, Jinyi, Fu, You, Guo, Yu, Wu, Yiran, Tan, Qiwen, Wang, Ling, Liu, Junlin, Jiang, Longquan, Fan, Zhongbo, Pei, Yuan, Yu, Jingyi, Cheng, Jianjun, Zhao, Suwen, Hao, Xiaojiang
Source: Science (pre-March 2025). 9/16/2022, Vol. 377 Issue 6612, p1298-1304. 7p. 5 Color Photographs.
Subjects: Taste receptors, Strychnine, G protein coupled receptors, Bitterness (Taste), Taste perception
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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
  Group: Ti
  Data: Structural basis for strychnine activation of human bitter taste receptor TAS2R46.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Xu%2C+Weixiu%22">Xu, Weixiu</searchLink><br /><searchLink fieldCode="AR" term="%22Wu%2C+Lijie%22">Wu, Lijie</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Shenhui%22">Liu, Shenhui</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Xiao%22">Liu, Xiao</searchLink><br /><searchLink fieldCode="AR" term="%22Cao%2C+Xiaoling%22">Cao, Xiaoling</searchLink><br /><searchLink fieldCode="AR" term="%22Zhou%2C+Cui%22">Zhou, Cui</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Jinyi%22">Zhang, Jinyi</searchLink><br /><searchLink fieldCode="AR" term="%22Fu%2C+You%22">Fu, You</searchLink><br /><searchLink fieldCode="AR" term="%22Guo%2C+Yu%22">Guo, Yu</searchLink><br /><searchLink fieldCode="AR" term="%22Wu%2C+Yiran%22">Wu, Yiran</searchLink><br /><searchLink fieldCode="AR" term="%22Tan%2C+Qiwen%22">Tan, Qiwen</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Ling%22">Wang, Ling</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Junlin%22">Liu, Junlin</searchLink><br /><searchLink fieldCode="AR" term="%22Jiang%2C+Longquan%22">Jiang, Longquan</searchLink><br /><searchLink fieldCode="AR" term="%22Fan%2C+Zhongbo%22">Fan, Zhongbo</searchLink><br /><searchLink fieldCode="AR" term="%22Pei%2C+Yuan%22">Pei, Yuan</searchLink><br /><searchLink fieldCode="AR" term="%22Yu%2C+Jingyi%22">Yu, Jingyi</searchLink><br /><searchLink fieldCode="AR" term="%22Cheng%2C+Jianjun%22">Cheng, Jianjun</searchLink><br /><searchLink fieldCode="AR" term="%22Zhao%2C+Suwen%22">Zhao, Suwen</searchLink><br /><searchLink fieldCode="AR" term="%22Hao%2C+Xiaojiang%22">Hao, Xiaojiang</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 9/16/2022, Vol. 377 Issue 6612, p1298-1304. 7p. 5 Color Photographs.
– Name: Subject
  Label: Subjects
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  Data: <searchLink fieldCode="DE" term="%22Taste+receptors%22">Taste receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Strychnine%22">Strychnine</searchLink><br /><searchLink fieldCode="DE" term="%22G+protein+coupled+receptors%22">G protein coupled receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Bitterness+%28Taste%29%22">Bitterness (Taste)</searchLink><br /><searchLink fieldCode="DE" term="%22Taste+perception%22">Taste perception</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=159131235
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        Value: 10.1126/science.abo1633
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        Text: English
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        Type: general
      – SubjectFull: Strychnine
        Type: general
      – SubjectFull: G protein coupled receptors
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      – SubjectFull: Bitterness (Taste)
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              Text: 9/16/2022
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