Fig. 1: Cryo-EM complex structures of MC4R–Gs bound with NDP-α-MSH and setmelanotide.
From: Structures of active melanocortin-4 receptor–Gs-protein complexes with NDP-α-MSH and setmelanotide
a Sequence alignment of MC4R agonists and antagonist SHU9119. For comparison and simplification, a ligand unifying numbering system is introduced based on the α-MSH core HxRW motif and indicated in superscript for each peptide residue. b, c Cryo-EM densities of MC4R–Gs complexes stabilized by Nb35 and bound agonists, displayed from mirrored perspectives. Gβ, dark blue; Gγ, red; Nb35, yellow. d Superposition of both agonists. e, f Comparison between SHU9119-antagonized (blue) MC4R16 and the active-state structures, either from the cytoplasmic view (e) or from inside the membrane plane (f). Arrows indicate significant relative spatial differences of transmembrane helices (TM5, TM6, and TM7).
