Unraveling the molecular architecture of a G protein-coupled receptor/β-arrestin/Erk module complex

Sci Rep. 2015 Jun 1;5:10760. doi: 10.1038/srep10760.

Abstract

β-arrestins serve as signaling scaffolds downstream of G protein-coupled receptors, and thus play a crucial role in a plethora of cellular processes. Although it is largely accepted that the ability of β-arrestins to interact simultaneously with many protein partners is key in G protein-independent signaling of GPCRs, only the precise knowledge of these multimeric arrangements will allow a full understanding of the dynamics of these interactions and their functional consequences. However, current experimental procedures for the determination of the three-dimensional structures of protein-protein complexes are not well adapted to analyze these short-lived, multi-component assemblies. We propose a model of the receptor/β-arrestin/Erk1 signaling module, which is consistent with most of the available experimental data. Moreover, for the β-arrestin/Raf1 and the β-arrestin/ERK interactions, we have used the model to design interfering peptides and shown that they compete with both partners, hereby demonstrating the validity of the predicted interaction regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestins / chemistry*
  • Arrestins / metabolism
  • Extracellular Signal-Regulated MAP Kinases / chemistry*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • MAP Kinase Kinase 1 / chemistry
  • MAP Kinase Kinase 1 / metabolism
  • Models, Molecular*
  • Molecular Docking Simulation
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins pp60(c-src) / chemistry
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • beta-Arrestins
  • src Homology Domains

Substances

  • Arrestins
  • Multiprotein Complexes
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • Proto-Oncogene Proteins pp60(c-src)
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human