Towards an understanding of S100A8 and S100A9 post‐translational regulation

S100A8 and S100A9 are small (10.8 kDa and 13.2 kDa), single-domain, α-helical proteins belonging to the S100 family of Ca2+ -binding proteins. They are moonlighting proteins exerting many important intra- and extracellular, physiological and pathophysiological roles related to signaling, regulation and defense. It has been a long-term challenge to distinguish the properties of different S100A8 and S100A9 proteoforms related to various biological functions in the human organism. Many limitations have been encountered in the characterization of their structures. Most structural studies were performed for either truncated or mutated variants, especially with removed cysteine residues. The single cysteine's of S100A8 and S100A9 are reactive, and in vivo undergo post-translational modifications (PTMs) i.e., S-glutathionylation or S-nitrosylation, regulating the proteins activities in inflammatory processes. In this work, we aimed to provide the missing conformational analysis for full length, non-mutated S100A8 and S100A9 proteins. using, in particular HDX-MS method. Our poster presents study of consequences of S-nitrosylation and S-glutathionylation on cysteines reactivity and structural conformation of S100A8 and S100A9 proteins.