Fig. 6: Conformation of H8.
a, b Structural comparison of the inactive (blue) and active (salmon) states of DP1 with the inactive state of β2AR (aquamarine), viewed within the lipid membrane (a) and from the intracellular side (b). H8 flips over by almost 180° within the plane of the membrane in DP1 contacting TM6, compared to the classical orientation of H8 in β2AR contacting TM1. c Salt bridge between R3328.52 and D2626.32 in DP1, and two residues from the classical F8.50xxxF8.54 motif in β2AR overlapping with the side chain of R3278.47 in DP1. d Structural comparison between prostanoid receptors showing orientations of their H8: inactive DP1 (blue, PDB: 9EKH), inactive β2AR (aquamarine, PDB: 2RH1), inactive EP4 (gray, PDB: 5YWY), inactive TP (violet, PDB: 6IIU), active EP2 (yellow, PDB: 7CX2), active EP4 (orange, PDB: 7D7M), active FP (pink, PDB: 8IUK), active IP (tan, PDB: 8X7A). e Multiple sequence alignment of H8 comparing β2AR with prostanoid receptors. f β-arrestin2 recruitment Tango assay showing the concentration-response signal for WT DP1 and several mutants involved in receptor activation and stabilization of H8. The signal is normalized to represent the percent increase above basal. Data points correspond to means ± SEM for three biologically independent experiments conducted in triplicates. The corresponding Emax and EC50 values are shown in Supplementary Table 5. Source Data are provided as a Source data file.
