The S100 protein family
S100 family proteins and their complexes with many interactions partners are mostly involved in tumors and metastasis. Our NMR spectroscopic studies are targeted towards the S100A4 and S100B members.
The asymmetric complex of Ca2+-loaded S100A4 with non-muscle myosin IIA strongly promotes metastasis, has high stability and highly increased Ca2+-affinity. Backbone dynamics reveals slow time-scale local motions in the H1 helices of the homodimeric S100A4. This motion diminishes in the complexed form and can be one reason of the increased dimer stability. Different mobilities in the Ca2+-coordinating EF-hand sites indicate that they communicate by an allosteric mechanism operating through changes in protein dynamics that must be responsible for the elevated Ca2+-affinity.
We showed that the activation of the entire C-terminal random coil of the homodimer S100A4 protein can play a role in mediating interaction with selected partner proteins. Pulsed field gradient NMR measurements show that the hydrodynamic radius in the wild-type protein increases upon Ca2+ binding while the radius of the C-terminal tail truncated mutant does not change. This finding was strengthened by SAXS measurements and MD-simulation.
The S100B interaction with calcium/calmodulin-dependent protein kinase (CaMK)-type domain of Ribosomal S6 Kinase 1 (RSK1) can facilitate therapeutic targeting of melanomas, because S100B inhibits the first phosphorylation event on RSK1 in the MAPK pathway responsible for cell growth in malignant melanomas. Therefore, we investigated and characterized the structure of S100B-RSK1 by NMR spectroscopy, christallography and SAXS. The synergy of these methods reveal that S100B forms a "fuzzy" complex with RSK1 peptide ligands.
Dr. László Nyitray, Department of Biochemistry, Eötvös Loránd University, Budapest
Dr. Attila Reményi, Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest
Annette Duelli , Bence Kiss , Ida Lundholm , Andrea Bodor , Maxim V. Petoukhov , Dmitri I. Svergun , László Nyitray , Gergely Katona
The C-terminal random coil region tunes the Ca²⁺-binding affinity of S100A4 through conformational activation
PLoS One 9(5):e97654 | DOI: 10.1371/journal.pone.0097654 | PMID: 24830809 (2014) Kivonat
Oscar Parravicini , Csaba Somlai , Sebastián A. Andujar , Adriana D. Garro , Beatriz Lima , Alejandro Tapia , Gabriela Feresin , András Perczel , Gábor Tóth , Javier López Cascales , Ana M. Rodríguez , Ricardo D. Enriz
Small Peptides Derived from Penetratin as Antibacterial Agents
Arch.Pharm.Chem.Life.Sci. 349:242-251. DOI: 10.1002/ardp.201500419 (2016) Kivonat
Pál Stráner , Nóra Taricska , Mária Szabó , Gábor K. Tóth , András Perczel
Bacterial expression and/or solid phase peptide synthesis of 20-40 amino acid long polypeptides and miniproteins, the case study of Class B GPCR ligands
Curr. Prot. Pept. Sci. 17(2):147-155. DOI: 10.2174/1389203716666151102105215 | PMID: 26521952 (2016) Kivonat