title: Membrane potentials regulating GPCRs: insights from experiments and molecular dynamics simulations.
abstract: G-protein coupled receptors (GPCRs) form the largest class of membrane proteins in humans and the targets of most present drugs. Membrane potential is one of the defining characteristics of living cells. Recent work has shown that the membrane voltage, and changes thereof, modulates signal transduction and ligand binding in GPCRs. As it may allow differential signalling patterns depending on tissue, cell type, and the excitation status of excitable cells, GPCR voltage sensitivity could have important implications for their pharmacology. This review summarises recent experimental insights on GPCR voltage regulation and the role of molecular dynamics simulations in identifying the structural basis of GPCR voltage-sensing. We discuss the potential significance for drug design on GPCR targets from excitable and non-excitable cells.
authors.affiliation: Physics, School of Science and Engineering, University of Dundee, Nethergate Dundee DD1 4NH, UK; Computational Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Owen N
authors.initials: ON
authors.lastname: Vickery
authors.affiliation: Institute of Complex Systems, Zelluläre Biophysik (ICS-4), Forschungszentrum Jülich, 52428 Jülich, Germany.
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Machtens
authors.affiliation: Physics, School of Science and Engineering, University of Dundee, Nethergate Dundee DD1 4NH, UK; Computational Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. Electronic address: u.zachariae@dundee.ac.uk.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zachariae
mesh_terms: D015195:Drug Design; D006801:Humans; D008024:Ligands; D008564:Membrane Potentials; D056004:Molecular Dynamics Simulation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled