Cytokine, S100 Protein, S100P, Protein–protein Interaction
Digital Object Identifier (DOI)
S100 proteins are multifunctional calcium-binding proteins of vertebrates that act intracellularly, extracellularly, or both, and are engaged in the progression of many socially significant diseases. Their extracellular action is typically mediated by the recognition of specific receptor proteins. Recent studies indicate the ability of some S100 proteins to affect cytokine signaling through direct interaction with cytokines. S100P was shown to be the S100 protein most actively involved in interactions with some four-helical cytokines. To assess the selectivity of the S100P protein binding to four-helical cytokines, we have probed the interaction of Ca2+-bound recombinant human S100P with a panel of 32 four-helical human cytokines covering all structural families of this fold, using surface plasmon resonance spectroscopy. A total of 22 cytokines from all families of four-helical cytokines are S100P binders with the equilibrium dissociation constants, Kd, ranging from 1 nM to 3 µM (below the Kd value for the S100P complex with the V domain of its conventional receptor, receptor for advanced glycation end products, RAGE). Molecular docking and mutagenesis studies revealed the presence in the S100P molecule of a cytokine-binding site, which overlaps with the RAGE-binding site. Since S100 binding to four-helical cytokines inhibits their signaling in some cases, the revealed ability of the S100P protein to interact with ca. 71% of the four-helical cytokines indicates that S100P may serve as a poorly selective inhibitor of their action.
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Citation / Publisher Attribution
International Journal of Molecular Sciences, v. 39, issue 19, art. 12000
Scholar Commons Citation
Kazakov, Alexey S.; Deryusheva, Eugenia I.; Permyakova, Maria E.; Sokolov, Andrey S.; Rastrygina, Victoria A.; Uversky, Vladimir N.; Permyakov, Eugene A.; and Permyakov, Sergei E., "Calcium-bound S100P Protein Is a Promiscuous Binding Partner of the Four-helical Cytokines" (2022). Molecular Medicine Faculty Publications. 1009.