EMD-19745

Single-particle
2.97 Å
EMD-19745 Deposition: 25/02/2024
Map released: 08/01/2025
Last modified: 08/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-19745

TAS2R14 receptor bound to flufenamic acid and gustducin

EMD-19745

Single-particle
2.97 Å
EMD-19745 Deposition: 25/02/2024
Map released: 08/01/2025
Last modified: 08/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Human Taste receptor type 2 member 14 in complex with G-proteins

Deposition Authors: Matzov D, Peri L , Niv M, Shalev Benami M
A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR.
PUBMED: 39557861
DOI: doi:10.1038/s41467-024-54157-6
ISSN: 2041-1723
Abstract:
Bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs) expressed orally and extraorally, elicit signaling in response to a large set of tastants. Among 25 functional TAS2Rs encoded in the human genome, TAS2R14 is the most promiscuous, and responds to hundreds of chemically diverse ligands. Here we present the cryo-electron microscopy (cryo-EM) structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to flufenamic acid (FFA), a clinically approved nonsteroidal anti-inflammatory drug. The structure reveals an unusual binding mode, where two copies of FFA are bound at distinct pockets: one at the canonical receptor site within the trans-membrane bundle, and the other in the intracellular facet, bridging the receptor with gustducin. Together with a pocket-specific BRET-based ligand binding assay, these results illuminate bitter taste signaling and provide tools for a site-targeted compound design.