Molecular mechanism of phosphorylation-dependent arrestin activation

Curr Opin Struct Biol. 2014 Dec;29:143-51. doi: 10.1016/j.sbi.2014.07.006. Epub 2014 Dec 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Arrestins / chemistry*
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphopeptides / chemistry
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Receptors, G-Protein-Coupled / chemistry*

Substances

  • Arrestins
  • Phosphopeptides
  • Receptors, G-Protein-Coupled