title: C-edge loops of arrestin function as a membrane anchor.
abstract: G-protein-coupled receptors are membrane proteins that are regulated by a small family of arrestin proteins. During formation of the arrestin-receptor complex, arrestin first interacts with the phosphorylated receptor C terminus in a pre-complex, which activates arrestin for tight receptor binding. Currently, little is known about the structure of the pre-complex and its transition to a high-affinity complex. Here we present molecular dynamics simulations and site-directed fluorescence experiments on arrestin-1 interactions with rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor. Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the membrane, and we show that these interactions are distinct in the pre-complex and high-affinity complex in regard to their conformation and orientation. Our results expand current knowledge of C-edge structure and further illuminate the conformational transitions that occur in arrestin along the pathway to tight receptor binding.
authors.affiliation: Institute of Medical Physics and Biophysics (CC2), Charité Medical University, Charitéplatz 1, Berlin 10117, Germany.
authors.forename: Ciara C M
authors.initials: CC
authors.lastname: Lally
authors.affiliation: Institute of Medical Physics and Biophysics (CC2), Charité Medical University, Charitéplatz 1, Berlin 10117, Germany.
authors.forename: Brian
authors.initials: B
authors.lastname: Bauer
authors.affiliation: Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Pompeu Fabra University, Hospital del Mar Medical Research Institute, Carrer del Dr. Aiguader, 88, Barcelona 08003, Spain.
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
authors.affiliation: Institute of Medical Physics and Biophysics (CC2), Charité Medical University, Charitéplatz 1, Berlin 10117, Germany.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Sommer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D019390:Arrestins; D046912:Multiprotein Complexes; C000607302:arrestin 1 protein, mouse; D012243:Rhodopsin