Fig. 1: Cryo-EM structure of active-state GPR61-G protein complex.
From: An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism
a Map (left) and model (right) of active-state GPR61-G protein complex with scFv16, colored by subunit. Grey lines indicate the position of the plasma membrane. b Highlighted by inset from a, left panel. Left panel, Extracellular face of GPR61, with ECL2 (extracellular loop 2) highlighted in orange and residues participating in the conserved disulfide shown in stick representation. Right panel, The orthosteric pocket of GPR61 is highlighted with a red dotted line. Key residues of ECL2 (orange) blocking access to the lower portion of the pocket are shown in stick representation. Transmembrane helices are labeled with numbered TM notations. c–f. Key residues involved in GPR61-Gαs interaction, corresponding to the highlighted region of A, right panel. c Polar interactions d Hydrogen bond network underlying selectivity for Gαs. e D/ERY motif hydrophobic stacking interactions with Gαs. f Hydrophobic interactions. g A disulfide bridging GPR61 TM6 and TM7, with nearby motifs involved in activation switching highlighted.
