Fig. 7: Biochemical studies and GaMD simulations of the stability of the complexes of β1-AR and Gs when bound with a full agonist, a partial agonist, or a very weak partial agonist.
From: Structures of β1-adrenergic receptor in complex with Gs and ligands of different efficacies
a A schematic diagram represents the chemical process from BODIPY-GTPγS binding to the complex of ligand–receptor–Gα(nucleotide-free)–Gβγ), leading to the formation of the transient R–G(BODIPY-GTPγS) bound complex and the subsequent complex disassembly. b–e BODIPY-GTPγS binding to the transition state complex in the presence of isoproterenol (b), dobutamine (c), or cyanopindolol (d). Units reported as relative fluorescent units (RFU). One representative experiment from five or six independent experiments with similar results is shown for each case. e Summary of the half-life values. Data are shown as mean ± SD of five or six independent experiments. Two-sided P values are from Student’s t-test. f–h Ligand-dependent structural dynamics of β1-AR in the absence of Gs. The distance between the cytoplasmic ends of TM3 and TM6 (measured as the distance between the Cα atoms of Arg1393.50 and Leu2896.34) is calculated over the indicated time. Three GaMD simulations (black, red, blue) were performed. Lines depict the running average over 2 ns. The top dash lines indicate the distance observed in the cryo-EM structures, and the bottom dash lines indicate the distance observed in the inactive β1-AR (PDB 4GPO).
