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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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003754 |
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| Summary: | 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. |
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| ISSN: | 2211-1247 |