To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Structural basis of Ribos… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

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.

Journal article
Authors Gergö Gógl
Anita Alexa
Bence Kiss
Gergely Katona
Mihály Kovács
Andrea Bodor
Attila Reményi
László Nyitray
Published in The Journal of biological chemistry
Volume 291
Issue 1
Pages 11-27
ISSN 1083-351X
Publication year 2016
Published at Department of Chemistry and Molecular Biology
Pages 11-27
Language en
Links dx.doi.org/10.1074/jbc.M115.684928
Keywords 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)
Subject categories Structural Biology, Biochemistry

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.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?