Energy Landscapes Reveal Agonist Control of G Protein-Coupled Receptor Activation via Microswitches.

ABSTRACT: Agonist binding to G protein-coupled receptors (GPCRs) leads to conformational changes in the transmembrane region that activate cytosolic signaling pathways. Although high-resolution structures of different receptor states are available, atomistic details of allosteric signaling across the membrane remain elusive. We calculated free energy landscapes of β₂ adrenergic receptor activation using atomistic molecular dynamics simulations in an optimized string of swarms framework, which shed new light on how microswitches govern the equilibrium between conformational states. Contraction of the extracellular binding site in the presence of the agonist BI-167107 is obligatorily coupled to conformational changes in a connector motif located in the core of the transmembrane region. The

SUBMITTER: Fleetwood O 

PROVIDER: S-EPMC7307880 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature