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Göteborgs universitets publikationer

Structural basis of Ribosomal S6 Kinase 1 (RSK1) inhibition by S100B Protein: modulation of the Extracellular Signal-regulated Kinase (ERK) signaling cascade in a calcium-dependent way.

Författare och institution:
Gergö Gógl (-); Anita Alexa (-); Bence Kiss (-); Gergely Katona (Institutionen för kemi och molekylärbiologi); Mihály Kovács (-); Andrea Bodor (-); Attila Reményi (-); László Nyitray (-)
Publicerad i:
The Journal of biological chemistry, 291 ( 1 ) s. 11-27
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Mitogen-activated protein kinases (MAPK) promote MAPK activated protein kinase (MAPKAPK) activation. In the MAPK pathway responsible to cell growth, ERK2 initiates the first phosphorylation event on RSK1, which is inhibited by calcium-binding S100 proteins in malignant melanomas. Here we present a detailed in vitro biochemical and structural characterization of the S100B-RSK1 interaction. The calcium-dependent binding of S100B to the calcium/calmodulin dependent protein kinase (CaMK)-type domain of RSK1 is reminiscent to 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 CaMK domain containing protein kinases. Our crystallographic, small angle X-ray scattering (SAXS) 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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Biologiska vetenskaper ->
Biologiska vetenskaper ->
Biokemi och molekylärbiologi ->
calcium, crystal structure, extracellular-signal-regulated kinase (ERK), kinetics, melanoma, mitogen-activated protein kinase (MAPK), nuclear magnetic resonance (NMR), RSK, S100 proteins, small-angle X-ray scattering (SAXS)
Postens nummer:
Posten skapad:
2015-12-02 17:34
Posten ändrad:
2016-02-17 15:42

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