How GPCR Phosphorylation Patterns Orchestrate Arrestin-Mediated Signaling.

ABSTRACT: Binding of arrestin to phosphorylated G-protein-coupled receptors (GPCRs) controls many aspects of cell signaling. The number and arrangement of phosphates may vary substantially for a given GPCR, and different phosphorylation patterns trigger different arrestin-mediated effects. Here, we determine how GPCR phosphorylation influences arrestin behavior by using atomic-level simulations and site-directed spectroscopy to reveal the effects of phosphorylation patterns on arrestin binding and conformation. We find that patterns favoring binding differ from those favoring activation-associated conformational change. Both binding and conformation depend more on arrangement of phosphates than on their total number, with phosphorylation at different positions sometimes exerting opposite effects. Ph

SUBMITTER: Latorraca NR 

PROVIDER: S-EPMC7901245 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature