Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR
Summary: The human perception of bitterness is mediated by type 2 taste receptors (TAS2Rs), which recognize a broad array of bitter substances with distinct chemical properties. TAS2R16 exhibits a pronounced selectivity for β-glucoside-moiety-containing compounds, such as salicin from willow bark. H...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003754 |
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| author | Xin Wang Cui Zhou Weizhen Ao Lijie Wu Yiran Wu Weixiu Xu Shenhui Liu Qiwen Tan Ling Wang Fei Zhao Junlin Liu Yuan Pei Suwen Zhao Tian Hua |
| author_facet | Xin Wang Cui Zhou Weizhen Ao Lijie Wu Yiran Wu Weixiu Xu Shenhui Liu Qiwen Tan Ling Wang Fei Zhao Junlin Liu Yuan Pei Suwen Zhao Tian Hua |
| author_sort | Xin Wang |
| collection | DOAJ |
| description | Summary: The human perception of bitterness is mediated by type 2 taste receptors (TAS2Rs), which recognize a broad array of bitter substances with distinct chemical properties. TAS2R16 exhibits a pronounced selectivity for β-glucoside-moiety-containing compounds, such as salicin from willow bark. However, the molecular mechanism of moiety-specific recognition and receptor activation in TAS2R16 remains unclear. Here, we present cryoelectron microscopy structures of the salicin-activated human TAS2R16 complexed with gustducin and Gi1 and Gi2 proteins. The binding mode of salicin with TAS2R16 and the specific interactions of the β-D-glucopyranoside moiety are detailed. Together with molecular docking and mutagenesis data, this study uncovers the structural underpinnings of TAS2R16’s group-specific recognition, receptor activation, and subsequent gustducin and Gi protein coupling. These findings advance our understanding of human bitter taste receptors and provide a foundation for structural modifications of bitter glycosides, opening potential therapeutic applications. |
| format | Article |
| id | doaj-art-c621d7236c604a32a7f87be45d533d5d |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-c621d7236c604a32a7f87be45d533d5d2025-08-20T02:24:45ZengElsevierCell Reports2211-12472025-05-0144511560410.1016/j.celrep.2025.115604Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCRXin Wang0Cui Zhou1Weizhen Ao2Lijie Wu3Yiran Wu4Weixiu Xu5Shenhui Liu6Qiwen Tan7Ling Wang8Fei Zhao9Junlin Liu10Yuan Pei11Suwen Zhao12Tian Hua13iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Lingang Laboratory, Shanghai 200031, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Corresponding authorSummary: The human perception of bitterness is mediated by type 2 taste receptors (TAS2Rs), which recognize a broad array of bitter substances with distinct chemical properties. TAS2R16 exhibits a pronounced selectivity for β-glucoside-moiety-containing compounds, such as salicin from willow bark. However, the molecular mechanism of moiety-specific recognition and receptor activation in TAS2R16 remains unclear. Here, we present cryoelectron microscopy structures of the salicin-activated human TAS2R16 complexed with gustducin and Gi1 and Gi2 proteins. The binding mode of salicin with TAS2R16 and the specific interactions of the β-D-glucopyranoside moiety are detailed. Together with molecular docking and mutagenesis data, this study uncovers the structural underpinnings of TAS2R16’s group-specific recognition, receptor activation, and subsequent gustducin and Gi protein coupling. These findings advance our understanding of human bitter taste receptors and provide a foundation for structural modifications of bitter glycosides, opening potential therapeutic applications.http://www.sciencedirect.com/science/article/pii/S2211124725003754CP: Molecular biology |
| spellingShingle | Xin Wang Cui Zhou Weizhen Ao Lijie Wu Yiran Wu Weixiu Xu Shenhui Liu Qiwen Tan Ling Wang Fei Zhao Junlin Liu Yuan Pei Suwen Zhao Tian Hua Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR Cell Reports CP: Molecular biology |
| title | Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR |
| title_full | Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR |
| title_fullStr | Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR |
| title_full_unstemmed | Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR |
| title_short | Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR |
| title_sort | structural basis of β glucopyranoside salicin recognition by a human bitter taste gpcr |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003754 |
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