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  • Distinct G protein-coupled ...
    Mayer, Daniel; Damberger, Fred F; Samarasimhareddy, Mamidi; Feldmueller, Miki; Vuckovic, Ziva; Flock, Tilman; Bauer, Brian; Mutt, Eshita; Zosel, Franziska; Allain, Frédéric H T; Standfuss, Jörg; Schertler, Gebhard F X; Deupi, Xavier; Sommer, Martha E; Hurevich, Mattan; Friedler, Assaf; Veprintsev, Dmitry B

    Nature communications, 03/2019, Letnik: 10, Številka: 1
    Journal Article

    Cellular functions of arrestins are determined in part by the pattern of phosphorylation on the G protein-coupled receptors (GPCRs) to which arrestins bind. Despite high-resolution structural data of arrestins bound to phosphorylated receptor C-termini, the functional role of each phosphorylation site remains obscure. Here, we employ a library of synthetic phosphopeptide analogues of the GPCR rhodopsin C-terminus and determine the ability of these peptides to bind and activate arrestins using a variety of biochemical and biophysical methods. We further characterize how these peptides modulate the conformation of arrestin-1 by nuclear magnetic resonance (NMR). Our results indicate different functional classes of phosphorylation sites: 'key sites' required for arrestin binding and activation, an 'inhibitory site' that abrogates arrestin binding, and 'modulator sites' that influence the global conformation of arrestin. These functional motifs allow a better understanding of how different GPCR phosphorylation patterns might control how arrestin functions in the cell.