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Open AccessArticle

Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins

1
Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Institutskaya str., 7, 142290 Pushchino, Russia
2
Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland
3
Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9473; https://doi.org/10.3390/ijms21249473
Received: 25 November 2020 / Revised: 10 December 2020 / Accepted: 11 December 2020 / Published: 13 December 2020
(This article belongs to the Special Issue Protein Structure Dynamics and Function)
Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca2+-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca2+-dependent binding to IFN-β with equilibrium dissociation constants, Kd, of 0.04–1.5 µM for their Ca2+-bound homodimeric forms. Calcium depletion abolishes the S100—IFN-β interactions. Monomerization of S100A1/A4/A6 decreases Kd values down to 0.11–1.0 nM. Interferon-α is unable of binding to the S100 proteins studied. S100A1/A4 proteins inhibit IFN-β-induced suppression of MCF-7 cells viability. The revealed direct influence of specific S100 proteins on IFN-β activity uncovers a novel regulatory role of particular S100 proteins, and opens up novel approaches to enhancement of therapeutic efficacy of IFN-β. View Full-Text
Keywords: cytokine; interferon; S100 protein; protein–protein interaction; cancer cytokine; interferon; S100 protein; protein–protein interaction; cancer
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MDPI and ACS Style

Kazakov, A.S.; Sofin, A.D.; Avkhacheva, N.V.; Denesyuk, A.I.; Deryusheva, E.I.; Rastrygina, V.A.; Sokolov, A.S.; Permyakova, M.E.; Litus, E.A.; Uversky, V.N.; Permyakov, E.A.; Permyakov, S.E. Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins. Int. J. Mol. Sci. 2020, 21, 9473. https://doi.org/10.3390/ijms21249473

AMA Style

Kazakov AS, Sofin AD, Avkhacheva NV, Denesyuk AI, Deryusheva EI, Rastrygina VA, Sokolov AS, Permyakova ME, Litus EA, Uversky VN, Permyakov EA, Permyakov SE. Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins. International Journal of Molecular Sciences. 2020; 21(24):9473. https://doi.org/10.3390/ijms21249473

Chicago/Turabian Style

Kazakov, Alexey S.; Sofin, Alexander D.; Avkhacheva, Nadezhda V.; Denesyuk, Alexander I.; Deryusheva, Evgenia I.; Rastrygina, Victoria A.; Sokolov, Andrey S.; Permyakova, Maria E.; Litus, Ekaterina A.; Uversky, Vladimir N.; Permyakov, Eugene A.; Permyakov, Sergei E. 2020. "Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins" Int. J. Mol. Sci. 21, no. 24: 9473. https://doi.org/10.3390/ijms21249473

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