title: Biophysical Detection of Diversity and Bias in GPCR Function.
abstract: Guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) function in complexes with a range of molecules and proteins including ligands, G proteins, arrestins, ubiquitin, and other receptors. Elements of these complexes may interact constitutively or dynamically, dependent upon factors such as ligand binding, phosphorylation, and dephosphorylation. They may also be allosterically modulated by other proteins in a manner that changes temporally and spatially within the cell. Elucidating how these complexes function has been greatly enhanced by biophysical technologies that are able to monitor proximity and/or binding, often in real time and in live cells. These include resonance energy transfer approaches such as bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). Furthermore, the use of fluorescent ligands has enabled novel insights into allosteric interactions between GPCRs. Consequently, biophysical approaches are helping to unlock the amazing diversity and bias in G protein-coupled receptor signaling.
authors.affiliation: Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia , Perth, WA , Australia.
authors.forename: Werner C
authors.initials: WC
authors.lastname: Jaeger
authors.affiliation: Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia , Perth, WA , Australia.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Armstrong
authors.affiliation: Cell Signalling Research Group, School of Life Sciences, Queen's Medical Centre, University of Nottingham Medical School , Nottingham , UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hill
authors.affiliation: Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia , Perth, WA , Australia ; Dimerix Bioscience Pty Ltd , Perth, WA , Australia.
authors.forename: Kevin D G
authors.initials: KD
authors.lastname: Pfleger
keywords: BRET; FRET; GPCR; GPCR-HIT; Receptor-HIT; bioluminescence resonance energy transfer; fluorescence resonance energy transfer; heteromer