5CSF

S100B-RSK1 crystal structure A

Summary for 5CSF

• Entry DOI: 10.2210/pdb5csf/pdb
• Descriptor: Protein S100-B, Ribosomal protein S6 kinase alpha-1, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: complex, kinase, signaling, inhibitor, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P04271; Nucleus: Q15418
• Total number of polymer chains: 3
• Total formula weight: 28120.75

Authors

Gogl, G.,Nyitray, L. (deposition date: 2015-07-23, release date: 2015-11-11, Last modification date: 2024-05-08)

Primary citation

Gogl, G.,Alexa, A.,Kiss, B.,Katona, G.,Kovacs, M.,Bodor, A.,Remenyi, A.,Nyitray, L.
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.
J.Biol.Chem., 291:11-27, 2016

PubMed Abstract: 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.

PubMed: 26527685
DOI: 10.1074/jbc.M115.684928

Experimental method

X-RAY DIFFRACTION (2.4 Å)