9W0S

CryoEM structure of T2R46 in complex with Arteminisin and heterotrimeric G protein complex

This is a non-PDB format compatible entry.

Summary for 9W0S

• Entry DOI: 10.2210/pdb9w0s/pdb
• EMDB information: 65514
• 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, ... (5 entities in total)
• Functional Keywords: g protein-coupled receptor, bitter taste receptor 14, bitter taste receptor 46, ligand binding, signal transduction, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 128889.11

Authors

Tan, Q.,Yu, Y.,Han, X.,Zhao, Q.,Wu, B. (deposition date: 2025-07-24, release date: 2026-04-22, Last modification date: 2026-05-06)

Primary citation

Tan, Q.,Yu, Y.,Han, X.,Liu, K.,Han, S.,Wang, M.,Wei, Y.,Zhu, Y.,Chen, Q.,Ma, L.,Yi, C.,Chu, X.,Wu, B.,Zhao, Q.
Ligand binding modes of the bitter taste receptor T2R14 and T2R46.
Nat.Struct.Mol.Biol., 33:691-700, 2026

PubMed Abstract: Bitter taste receptors (T2Rs) are considered attractive drug targets. However, the ligand recognition and selectivity of these receptors remain elusive, hampering their drug development. Here we present seven structures of human T2R14 and T2R46 in apo or ligand-bound state. Combined with molecular docking and mutagenesis data, the structures reveal an extracellular ligand-binding site in T2R14 for most of its ligands, which is different from the intracellular binding site reported recently. In contrast, T2R46 exhibits a conserved binding pocket that accommodates various ligands with distinct interaction patterns. Furthermore, the second extracellular loop in T2R14 and T2R46 acts as a tethered agonist to potentially facilitate agonist response of these two receptors to the weak tastant agonists. These findings could accelerate drug discovery targeting T2Rs.

PubMed: 42009775
DOI: 10.1038/s41594-026-01786-8

Experimental method

ELECTRON MICROSCOPY (3.3 Å)