Potato aspartic proteases (StAPs) and their swaposin domain (StAsp-PSI) are proteins with cytotoxic activity
which involves plasma membrane destabilization. The ability of these proteins to produce cell death varies
with the cellular type. Therefore, StAPs and StAsp-PSI selective cytotoxicity could be attributed to the different
membrane lipid compositions of target cells. In this work we investigate the possible mechanism by
which StAPs and StAsp-PSI produce selective membrane destabilization. Results obtained from leakage assays
show that StAsp-PSI is a potent inducer of the leakage of LUVs containing anionic phospholipids, especially
those containing phosphatidylglycerol. Based in these results, we suggest that the cytotoxic activity of
StAsp-PSI on pathogenic microorganisms could be mediated by the attraction between the exposed positive
domains of StAsp-PSI and the negatively charged microorganism membrane. On the other hand, our circular
dichroism spectroscopic measurements and analysis by size exclusion chromatography and followed by electrophoresis,
indicate that hydrophobic environment is necessary to StAsp-PSI oligomerization and both
StAsp-PSI disulfide bounds and membrane with negative charged phospholipids are required by StAsp-PSI
to produce membrane destabilization and then induce cell death in tumors and microorganism cell targets.
Additionally, we demonstrate that the presence of cholesterol into the LUV membranes strongly diminishes
the capacity of StAsp-PSI to produce leakag