Cryo-EM structures of agonist-bound HCAR3-Gi1 and HCAR2-Gi1 complexes. (A) Schematic illustration of agonist selectivity to HCARs. (B-F) Cryo-EM maps and models in cartoon performance of HCAR3-Gi1 complexes in the presence of 6O (B), PLA (C), IBC293 (D), acifran (E), and HCAR2-Gi1 complex in the presence of acifran (F). Agonists are shown in stick representation, and corresponding electron densities are depicted as gray meshes. The maps and structural models are colored by subunits: Pale violet red, 6O-HCAR3; slate blue, PLA-HCAR3; medium sea green, IBC293-HCAR3; dodger blue, acifran-HCAR3; light salmon, acifran-HCAR2; light gray, Gαi; light blue, Gβ; light pink, Gγ; burly wood, scFv16; light green, 6O; cyan, PLA; khaki, IBC293; plum, acifran (HCAR3); medium aquamarine, acifran (HCAR2).
#Hydroxycarboxylic acid receptors HCAR2 & HCAR3 are key targets for treating #MetabolicDisorders. This study reports #cryoEM structures of #HCAR3 with several agonists, informing its ligand recognition & activation mechanism (& HCAR3/HCAR2 differences) @plosbiology.org 🧪 plos.io/48D365m