title: Molecular mechanism of phosphorylation-dependent arrestin activation.
abstract: The past years have seen tremendous progress towards understanding how arrestins recognize phosphorylated G protein-coupled receptors (GPCRs). Two arrestin crystal structures, one of a pre-activated splice variant and one bound to a GPCR phosphopeptide, provided insights into the conformational changes upon phosphate recognition. Scanning mutagenesis and spectroscopic studies complete the picture of arrestin activation and receptor binding. Most perspicuous is the C-tail exchange mechanism, by which the C-tail of arrestin is released from its basal conformation and replaced by the phosphorylated GPCR C-terminus. Three positively charged clusters could act as conserved arrestin phosphosensors. Variations in the pattern of phosphorylation in a GPCR and variations within the C-terminus of different GPCRs may encode specificity to arrestin subtypes and particular physiological responses.
authors.affiliation: Laboratory of Biomolecular Research, Paul Scherrer Institute, 5232 Villigen, Switzerland.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Ostermaier
authors.affiliation: Laboratory of Biomolecular Research, Paul Scherrer Institute, 5232 Villigen, Switzerland; Deparment of Biology, ETH Zurich, Wolfgang-Pauli-Str. 27, 8093 Zürich, Switzerland.
authors.forename: Gebhard F X
authors.initials: GF
authors.lastname: Schertler
authors.affiliation: Laboratory of Biomolecular Research, Paul Scherrer Institute, 5232 Villigen, Switzerland. Electronic address: joerg.standfuss@psi.ch.
authors.forename: Joerg
authors.initials: J
authors.lastname: Standfuss
mesh_terms: D000595:Amino Acid Sequence; D019390:Arrestins / Q000737:chemistry*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010748:Phosphopeptides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*
chemical_list: D019390:Arrestins; D010748:Phosphopeptides; D043562:Receptors, G-Protein-Coupled