Structure and interaction of VacA of Helicobacter pylori with a lipid membrane

In its mature form, the VacA toxin of Helicobacter pylori is a 95-kDa prote in which is released from the bacteria as a low-activity complex. This comp lex can be activated by low-pH treatment that parallels the activity of the toxin on target cells. VacA has been previously shown to insert itself int o lipid membranes and to induce anion-selective channels in planar lipid bi layers. Binding of VacA to lipid vesicles and its ability to induce calcein release from these vesicles were systematically compared as a function of pH. These two phenomena show a different pH-dependence, suggesting that the association with the lipid membrane may be a two-step mechanism. The secon dary and tertiary structure of VacA as a function of pH and the presence of lipid vesicles were investigated by Fourier-transform infrared spectroscop y. The secondary structure of VacA is identical whatever the pH and the pre sence of a lipid membrane, but the tertiary structure in the presence of a lipid membrane is dependent on pH, as evidenced by H/D exchange.