上海科技大学知识管理系统

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 cryo-electron microscopy structures of the salicin-activated human TAS2R16 complexed with gustducin, 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 proteins 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.