Fig. 1: An overall description of the TAS2R14 complex.
From: A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR
a Cryo-EM map of hTAS2R14 bound to the gustducin heterotrimer. TAS2R14 is colored green, gustducin in gold, the beta-gamma subunits are in teal and pink, respectively, and ScFV16 in white. b The chemical structure of FFA. The ring with the carboxylic moiety (red) is denoted A, and the ring with the trifluoromethyl moiety (green) is denoted B. The amino linker is highlighted in blue. c Cartoon representation of the TAS2R14 complex with FFA bound at the canonical (extracellular, extra-) and intracellular (intra-) sites. Colors are as in (a). d FFA docked in density for the canonical site. e FFA in density for the intracellular site. f Superposition of the canonical (orange) vs. the intracellular (gold) conformations of FFA indicating a 64° rotation of ring A relative to ring B. g Dose response curve for FFA in the mini-gustducin complementation assay designed for this study. Response is measured as nanoBiT dissociation normalized by basal activity of the wild-type receptor to FFA. Data are represented as mean ± SEM from three independent experiments performed in triplicate, indicating an EC50 of 46.26 ± 10 µM. h G-protein dissociation of TAS2R14 in response to FFA in HEK293 cells transiently co-expressing the wild-type receptor and TRUPATH biosensors for the full-length gustducin G-protein. Data are represented as mean ± SEM from seven independent experiments performed in triplicate, indicating an EC50 of 8.85 µM ± 2.52 µM. Source data are provided as a Source Data file.
