Desulfurisation Reactions in Human serum albumin associated with the formation of trans lipids in model mebranes

(a) Objectives Post-translational mutation of sulfur-containing amino acid in the protein sequence via radical damage is an interesting field of investigation. In addition, a single radical event on proteins could produce a reactive species able to damage another cell compartments. In this context we performed a characterization of Human Serum Albumin (HSA) damaged by reductive and oxidative reactive species. HSA is the most prominent protein in plasma and has many functions (i.e. from ligand-binding to antioxidant functions). It contains 6 Met and 35 Cys residues forming 17 disulfide bridges. (b) Methods The protein modifications were evaluated by combined Raman spectroscopy1 and mass spectrometry experiments2. Gamma-irradiation was used to simulate the endogenous formation of reductive species. Biomimetic models, containing protein and unsaturated lipid vesicles, were used to evaluate the role of sulfur-containing residues of proteins in translating the damage to other biomolecules. (c) Results - Reductive radical stress leads to the modification of Met to ?-aminobutyric acid (Aba), and of Cys to Ala. When these reactions were performed on HSA added to large unilamellar vesicles, desulfurisation yielded sulfur radicals able to induce a cis-trans isomerisation of lipids, analogously to other proteins.3 (d) Conclusions - This study can be useful to achieve an integrate vision of the free radical reactivities in a multifunctional system and highlights the role of trans lipids as "reporters" of protein damage at sulfur residues.