Fig. 3: CryoEM structures of δOR bound to bitopics.
From: Structure-guided design of partial agonists at an opioid receptor
A Overall architecture of δOR-C5-Quino Gαi1Gβ1Gγ2 complex and δOR-C6-Quino Gαi1Gβ1Gγ2 complex assembly. Density maps of the ligands are zoomed in. B Comparison of C6-Quino bound δOR with previous inactive- and active-state δOR structure. δOR-naltrindole (PDB ID 4N6H), δOR-deltorphin (PDB ID 8F7S) C Comparison of ligand binding pose between C6-Quino, naltrindole, and deltorphin. D δOR-C6-Quino interactions in the orthosteric binding pocket. E Residues with distinct effects on C6-Quino and DPDPE were characterized via mutation in BRET-G protein activation or arrestin recruitment assays. Potency and efficacy values are shown in Supplementary Table 9. Figures contain data as mean \(\pm \) SEM grouped from three independent biological replicates. Statistical significance analyses of potency changes between groups are compared using one-way ANOVA with Dunnett’s multiple-comparison test. Compared to WT, Gi1 Q105A: p = 0.003, K214A: p = 0.002; β-arrestin 2 Q105A: p = 0.002, K214A: p = 0.02.
