Complete complex model. The model can accommodate the presence of Clathrin and the SH2 domain of c-Src.
Color code : β-arrestin in grey, c-Src in blue, Raf1 in green, Mek1 in yellow, Erk1 in dark red.
Possible geometry of the complex including the β-arrestin/Erk1 module, including SH2 domain of c-Src (in orange) and clathrin (in marine blue).
Abstract• Introduction• Results• Discussion• Conclusion• Methods• Additional Information• References• Acknowledgements• Author information• Supplementary information
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.
Subject terms : Protein structure predictions Molecular modelling Signal processing Biochemical networks