TY - JOUR
T1 - Highly specific interaction of monomeric S100P protein with interferon beta
AU - Kazakov, AS
AU - Mayorov, SA
AU - Deryusheva, EI
AU - Avkhacheva, NV
AU - Denessiouk, Konstantin
AU - Denesyuk, Alexandre
AU - Rastrygina, VA
AU - Permyakov, EA
AU - [Unknown], Permyakov SE.
PY - 2020
Y1 - 2020
N2 - S100 proteins are EF-hand calcium-binding proteins of vertebrates exerting numerous intra- and extracellular actions and involved into multiple diseases. Some of S100 proteins serve as extracellular damage signals via interaction with receptors. Although several S100 proteins directly bind specific cytokines, this phenomenon remains underexplored. Using chemical crosslinking, intrinsic fluorescence and surface plasmon resonance spectroscopies, we show that S100P protein interacts with interferon beta (IFN-β) depending on calcium level and oligomeric state of S100P. Dimeric Ca2+-loaded S100P binds IFN-β with equilibrium dissociation constants, Kd, of 0.05-0.6 μM. S100P monomerization favors this interaction decreasing Kd values down to 0.3-2 nM. Calcium depletion drastically lowers S100P affinity to IFN-β. Other related EF-hand proteins studied (calmodulin, α-parvalbumin and S100G) do not bind IFN-β, thereby confirming selectivity of the S100P - IFN-β interaction. Crystal violet assay reveals that the S100P binding suppresses IFN-β cytotoxicity to MCF-7 breast cancer cells. Since several cancers (breast, colon, lung, liver, etc.) exhibit dysregulated functioning of S100P and IFN-β, their interaction could be relevant to the cancer progression and directed therapeutic interventions.
AB - S100 proteins are EF-hand calcium-binding proteins of vertebrates exerting numerous intra- and extracellular actions and involved into multiple diseases. Some of S100 proteins serve as extracellular damage signals via interaction with receptors. Although several S100 proteins directly bind specific cytokines, this phenomenon remains underexplored. Using chemical crosslinking, intrinsic fluorescence and surface plasmon resonance spectroscopies, we show that S100P protein interacts with interferon beta (IFN-β) depending on calcium level and oligomeric state of S100P. Dimeric Ca2+-loaded S100P binds IFN-β with equilibrium dissociation constants, Kd, of 0.05-0.6 μM. S100P monomerization favors this interaction decreasing Kd values down to 0.3-2 nM. Calcium depletion drastically lowers S100P affinity to IFN-β. Other related EF-hand proteins studied (calmodulin, α-parvalbumin and S100G) do not bind IFN-β, thereby confirming selectivity of the S100P - IFN-β interaction. Crystal violet assay reveals that the S100P binding suppresses IFN-β cytotoxicity to MCF-7 breast cancer cells. Since several cancers (breast, colon, lung, liver, etc.) exhibit dysregulated functioning of S100P and IFN-β, their interaction could be relevant to the cancer progression and directed therapeutic interventions.
U2 - 10.1016/j.ijbiomac.2019.12.039
DO - 10.1016/j.ijbiomac.2019.12.039
M3 - Article
SN - 0141-8130
VL - 143
SP - 633
EP - 639
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -