title: Unraveling the molecular architecture of a G protein-coupled receptor/β-arrestin/Erk module complex.
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.
authors.affiliation: 1] BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, 37041 Tours, France; IFCE, Nouzilly, F-37380 France [2] INRIA Nancy, 615 Rue du Jardin Botanique, Villers-lès-Nancy, 54600 France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourquard
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, 37041 Tours, France; IFCE, Nouzilly, F-37380 France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Landomiel
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, 37041 Tours, France; IFCE, Nouzilly, F-37380 France.
authors.forename: Eric
authors.initials: E
authors.lastname: Reiter
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, 37041 Tours, France; IFCE, Nouzilly, F-37380 France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Crépieux
authors.affiliation: INRIA Nancy, 615 Rue du Jardin Botanique, Villers-lès-Nancy, 54600 France.
authors.forename: David W
authors.initials: DW
authors.lastname: Ritchie
authors.affiliation: Bioinformatics group - AMIB INRIA - Laboratoire de Recherche en Informatique, Université Paris-Sud, Orsay, 91405 France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Azé
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, 37041 Tours, France; IFCE, Nouzilly, F-37380 France.
authors.forename: Anne
authors.initials: A
authors.lastname: Poupon
mesh_terms: D019390:Arrestins / Q000737:chemistry* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D000071557:beta-Arrestins; D018909:src Homology Domains
chemical_list: D019390:Arrestins; D046912:Multiprotein Complexes; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D016392:Proto-Oncogene Proteins pp60(c-src); D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human