Fig. 2: Ligand binding pocket in the inactive DP1 and recognition of inverse agonists.

a, b Cross-section through the receptor showing the ligand bound site and bound ligands for ONO2550289 (a) and ONO3030297 (b). Two gray lines indicate membrane boundaries as provided by the Orientation of Proteins in Membranes (OPM) database. c, d Details of DP1 residues’ interactions with ONO2550289 (c) and ONO3030297 (d). Hydrogen bonds and salt bridges are shown as red dashed lines. The ligands in (a–d) are shown as sticks with carbon atoms colored in chartreuse (ONO2550289) or cyan (ONO3030297). e, f Schematics of DP1 residues’ interactions with ONO2550289 (e) and ONO3030297 (f). Hydrogen bonds and salt bridges are shown in red dashed lines. g ONE-GO G_s signaling assay comparing the concentration-response signal induced by PGD2 at WT DP1 with the inactive cryo-EM construct (DP1_ICL3bRIL) and the inactive state stabilizing mutants C130^3.50R, H263^6.33A, and D319^7.49N. The data are normalized to the basal signal (set at 0%) and the maximal PGD2-induced signal at WT DP1 (set at 100%). Data points correspond to means ± SEM for three biologically independent experiments conducted in triplicates. The corresponding E_max and EC₅₀ values are shown in Supplementary Table 2. Source Data are provided as a Source data file.