5CSN: S100b-rsk1 Crystal Structure C

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.
PDB ID: 5CSNDownload
MMDB ID: 134115
PDB Deposition Date: 2015/7/23
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 2.95  Å
Source Organism:
Similar Structures:
Biological Unit for 5CSN: trimeric; determined by author and by software (PISA)
Molecular Components in 5CSN
Label Count Molecule
Proteins (3 molecules)
Protein S100-b(Gene symbol: S100B)
Molecule annotation
Ribosomal Protein S6 Kinase Alpha-1(Gene symbol: RPS6KA1)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB