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

Thomas Bourquard (1) , Flavie Landomiel (1) , Eric Reiter (1) , Pascale Crépieux (1) , David W. Ritchie (2) , Jérôme Azé (3, 4, 5) , Anne Poupon (1)

1 PRC - Physiologie de la reproduction et des comportements [Nouzilly]
2 CAPSID - Computational Algorithms for Protein Structures and Interactions
3 LRI - Laboratoire de Recherche en Informatique
4 AMIB - Algorithms and Models for Integrative Biology
5 ADVANSE - ADVanced Analytics for data SciencE

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.

Mots clés: Signal processing; Biochemical networks; Molecular modelling; Protein structure predictions

Domaines: Bio-informatique [q-bio.QM]

Thomas Bourquard, Flavie Landomiel, Eric Reiter, Pascale Crépieux, David W. Ritchie, et al.. Unraveling the molecular architecture of a G protein-coupled receptor/β-arrestin/Erk module complex. Scientific Reports, 2015, 5, pp.5:10760. ⟨10.1038/srep10760⟩. ⟨lirmm-01162594⟩