Fiche publication
Date publication
avril 2020
Journal
Structure (London, England : 1993)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr TRAVE Gilles
,
Dr NOMINE Yves
,
Dr GOGL Gergo
Tous les auteurs :
Gogl G, Jane P, Caillet-Saguy C, Kostmann C, Bich G, Cousido-Siah A, Nyitray L, Vincentelli R, Wolff N, Nomine Y, Sluchanko NN, Trave G
Lien Pubmed
Résumé
Protein-protein interaction motifs are often alterable by post-translational modifications. For example, 19% of predicted human PDZ domain-binding motifs (PBMs) have been experimentally proven to be phosphorylated, and up to 82% are theoretically phosphorylatable. Phosphorylation of PBMs may drastically rewire their interactomes, by altering their affinities for PDZ domains and 14-3-3 proteins. The effect of phosphorylation is often analyzed by performing "phosphomimetic" mutations. Here, we focused on the PBMs of HPV16-E6 viral oncoprotein and human RSK1 kinase. We measured the binding affinities of native, phosphorylated, and phosphomimetic variants of both PBMs toward the 266 human PDZ domains. We co-crystallized all the motif variants with a selected PDZ domain to characterize the structural consequence of the different modifications. Finally, we elucidated the structural basis of PBM capture by 14-3-3 proteins. This study provides novel atomic and interactomic insights into phosphorylatable dual specificity motifs and the differential effects of phosphorylation and phosphomimetic approaches.
Mots clés
14-3-3 proteins, PDZ domains, domain-motif interactions, phosphorylation, protein-protein interactions, quantitative interactomics
Référence
Structure. 2020 Apr 6;:
