Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation

Citation:

Mayer, D. ; Damberger, F. F. ; Samarasimhareddy, M. ; Feldmueller, M. ; Vuckovic, Z. ; Flock, T. ; Bauer, B. ; Mutt, E. ; Zosel, F. ; Allain, F. H. T. ; et al. Distinct G Protein-Coupled Receptor Phosphorylation Motifs Modulate Arrestin Affinity And Activation And Global Conformation. NATURE COMMUNICATIONS 2019, 10.

Date Published:

MAR 19

Abstract:

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.


 

Notes:

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Last updated on 09/04/2023