Fiche publication
Date publication
janvier 2022
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOGL Gergo
Tous les auteurs :
Alexa A, Sok P, Gross F, Albert K, Kobori E, Póti ÁL, Gógl G, Bento I, Kuang E, Taylor SS, Zhu F, Ciliberto A, Reményi A
Lien Pubmed
Résumé
The Kaposi's sarcoma associated herpesvirus protein ORF45 binds the extracellular signal-regulated kinase (ERK) and the p90 Ribosomal S6 kinase (RSK). ORF45 was shown to be a kinase activator in cells but a kinase inhibitor in vitro, and its effects on the ERK-RSK complex are unknown. Here, we demonstrate that ORF45 binds ERK and RSK using optimized linear binding motifs. The crystal structure of the ORF45-ERK2 complex shows how kinase docking motifs recognize the activated form of ERK. The crystal structure of the ORF45-RSK2 complex reveals an AGC kinase docking system, for which we provide evidence that it is functional in the host. We find that ORF45 manipulates ERK-RSK signaling by favoring the formation of a complex, in which activated kinases are better protected from phosphatases and docking motif-independent RSK substrate phosphorylation is selectively up-regulated. As such, our data suggest that ORF45 interferes with the natural design of kinase docking systems in the host.
Mots clés
Cell Line, Computational Biology, Crystallography, X-Ray, methods, Herpesvirus 8, Human, chemistry, Humans, Immediate-Early Proteins, chemistry, Mitogen-Activated Protein Kinase 1, chemistry, Phosphorylation, Ribosomal Protein S6 Kinases, 90-kDa, chemistry, Sarcoma, Kaposi, metabolism, Signal Transduction
Référence
Nat Commun. 2022 01 25;13(1):472
