Fig. 1. Overall structures of peptide agonist and small-molecule agonist-activated OX₂R.

a Structural formula of the small-molecule orexin agonist used in this study. b Concentration-dependent activation of OX₁R and OX₂R by OxB and compound 1. Half maximal effective concentrations represented as pEC₅₀ are: 4.45 ± 0.06 (OX₁R–compound 1), 8.28 ± 0.03 (OX₂R–compound 1), 6.09 ± 0.14 (OX₁R–OxB), and 7.17 ± 0.07 (OX₂R–OxB); error bars represent the standard error of the mean of n = 4 independent experiments for all except for OX₁R/compound 1, for which n = 5 independent experiments were performed. Data are presented as mean values ± s.e.m. c, d Structures of nucleotide-free OX₂R–G-protein complexes bound to OxB and compound 1, respectively, color-coded by subunit. Source data are provided as a Source Data file.