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TitleStructural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR.
Journal, issue, pagesCell Rep, Vol. 44, Issue 5, Page 115604, Year 2025
Publish dateMay 27, 2025
AuthorsXin 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 /
PubMed AbstractThe 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 ...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 G and G 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 G 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.
External linksCell Rep / PubMed:40261795
MethodsEM (single particle)
Resolution2.77 - 3.35 Å
Structure data

EMDB-62129, PDB-9k6l:
Cryo-EM structure of GPCR16-Gi2 complex
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-62484, PDB-9kpd:
Cryo-EM structure of GPCR16-miniGs complex
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-62485, PDB-9kpe:
Cryo-EM structure of GPCR16-GiH5 complex
Method: EM (single particle) / Resolution: 3.35 Å

EMDB-62486, PDB-9kpf:
Cryo-EM structure of GPCR16-Gi complex
Method: EM (single particle) / Resolution: 3.15 Å

Chemicals

ChemComp-SA0:
2-(hydroxymethyl)phenyl beta-D-glucopyranoside

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • streptococcus pneumoniae (bacteria)
KeywordsSIGNALING PROTEIN/IMMUNE SYSTEM / Tas2R16 / GPCR / Gi2 / Salicin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex / Complex

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