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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
2 CAPSID - Computational Algorithms for Protein Structures and Interactions
Inria Nancy - Grand Est, LORIA - AIS - Department of Complex Systems, Artificial Intelligence & Robotics
4 AMIB - Algorithms and Models for Integrative Biology
LIX - Laboratoire d'informatique de l'École polytechnique [Palaiseau], LRI - Laboratoire de Recherche en Informatique, UP11 - Université Paris-Sud - Paris 11, Inria Saclay - Ile de France
5 ADVANSE - ADVanced Analytics for data SciencE
LIRMM - Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier
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.
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Submitted on : Wednesday, June 10, 2015 - 9:45:57 PM
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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, Nature Publishing Group, 2015, 5, pp.5:10760. ⟨10.1038/srep10760⟩. ⟨lirmm-01162594⟩



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