Ligand Binding Ensembles Determine Graded Agonist Efficacies at a G Protein-coupled Receptor.

ABSTRACT: G protein-coupled receptors constitute the largest family of membrane receptors and modulate almost every physiological process in humans. Binding of agonists to G protein-coupled receptors induces a shift from inactive to active receptor conformations. Biophysical studies of the dynamic equilibrium of receptors suggest that a portion of receptors can remain in inactive states even in the presence of saturating concentrations of agonist and G protein mimetic. However, the molecular details of agonist-bound inactive receptors are poorly understood. Here we use the model of bitopic orthosteric/allosteric (i.e. dualsteric) agonists for muscarinic M2 receptors to demonstrate the existence and function of such inactive agonist·receptor complexes on a molecular level. Using all-atom molecular dy

SUBMITTER: Bock A 

PROVIDER: S-EPMC4965584 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature