9KPF

Cryo-EM structure of GPCR16-Gi complex

Summary for 9KPF

• Entry DOI: 10.2210/pdb9kpf/pdb
• EMDB information: 62486
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: gpcr, complex, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 232692.35

Authors

Wang, X.,Wu, L.J.,Hua, T.,Liu, Z.J. (deposition date: 2024-11-22, release date: 2025-04-02, Last modification date: 2025-10-15)

Primary citation

Wang, X.,Zhou, C.,Ao, W.,Wu, L.,Wu, Y.,Xu, W.,Liu, S.,Tan, Q.,Wang, L.,Zhao, F.,Liu, J.,Pei, Y.,Zhao, S.,Hua, T.
Structural basis of beta-glucopyranoside salicin recognition by a human bitter taste GPCR.
Cell Rep, 44:115604-115604, 2025

PubMed Abstract: 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.

PubMed: 40261795
DOI: 10.1016/j.celrep.2025.115604

Experimental method

ELECTRON MICROSCOPY (3.15 Å)