Institute for Biological Instrumentation of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Pushchino, Moscow Region 142290, Russia.
Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland; Pharmaceutical Sciences Laboratory, Pharmacy, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland.
Int J Biol Macromol. 2020 Jan 15;143:633-639. doi: 10.1016/j.ijbiomac.2019.12.039. Epub 2019 Dec 7.
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 Ca-loaded S100P binds IFN-β with equilibrium dissociation constants, K, of 0.05-0.6 μM. S100P monomerization favors this interaction decreasing K 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.
S100 蛋白是脊椎动物的 EF 手钙结合蛋白，具有多种细胞内和细胞外作用，并涉及多种疾病。一些 S100 蛋白作为细胞外损伤信号通过与受体相互作用。尽管一些 S100 蛋白直接结合特定的细胞因子，但这种现象仍未得到充分探索。我们使用化学交联、固有荧光和表面等离子体共振光谱法表明，S100P 蛋白与干扰素β（IFN-β）相互作用取决于钙水平和 S100P 的寡聚状态。二聚体 Ca 负载的 S100P 与 IFN-β的平衡解离常数 K 为 0.05-0.6 μM。S100P 单体化有利于这种相互作用，将 K 值降低至 0.3-2 nM。钙耗竭大大降低了 S100P 与 IFN-β的亲和力。研究的其他相关 EF 手蛋白（钙调蛋白、α-副肌球蛋白和 S100G）不与 IFN-β结合，从而证实了 S100P-IFN-β 相互作用的选择性。结晶紫测定表明，S100P 结合抑制了 IFN-β对 MCF-7 乳腺癌细胞的细胞毒性。由于几种癌症（乳腺癌、结肠癌、肺癌、肝癌等）表现出 S100P 和 IFN-β的失调功能，它们的相互作用可能与癌症的进展和靶向治疗干预有关。
