Fiche publication
Date publication
janvier 2016
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOGL Gergo
Tous les auteurs :
Gógl G, Alexa A, Kiss B, Katona G, Kovács M, Bodor A, Reményi A, Nyitray L
Lien Pubmed
Résumé
Mitogen-activated protein kinases (MAPK) promote MAPK-activated protein kinase activation. In the MAPK pathway responsible for cell growth, ERK2 initiates the first phosphorylation event on RSK1, which is inhibited by Ca(2+)-binding S100 proteins in malignant melanomas. Here, we present a detailed in vitro biochemical and structural characterization of the S100B-RSK1 interaction. The Ca(2+)-dependent binding of S100B to the calcium/calmodulin-dependent protein kinase (CaMK)-type domain of RSK1 is reminiscent of the better known binding of calmodulin to CaMKII. Although S100B-RSK1 and the calmodulin-CAMKII system are clearly distinct functionally, they demonstrate how unrelated intracellular Ca(2+)-binding proteins could influence the activity of the CaMK domain-containing protein kinases. Our crystallographic, small angle x-ray scattering, and NMR analysis revealed that S100B forms a "fuzzy" complex with RSK1 peptide ligands. Based on fast-kinetics experiments, we conclude that the binding involves both conformation selection and induced fit steps. Knowledge of the structural basis of this interaction could facilitate therapeutic targeting of melanomas.
Mots clés
RSK, S100 proteins, calcium, crystal structure, extracellular-signal-regulated kinase (ERK), kinetics, melanoma, mitogen-activated protein kinase (MAPK), nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS)
Référence
J Biol Chem. 2016 01 1;291(1):11-27
