title: Structure and interaction of VacA of Helicobacter pylori with a lipid membrane.
abstract: In its mature form, the VacA toxin of Helicobacter pylori is a 95-kDa protein which is released from the bacteria as a low-activity complex. This complex 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 into lipid membranes and to induce anion-selective channels in planar lipid bilayers. 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 secondary and tertiary structure of VacA as a function of pH and the presence of lipid vesicles were investigated by Fourier-transform infrared spectroscopy. The secondary structure of VacA is identical whatever the pH and the presence 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.
authors.affiliation: Centro di Ricerche IRIS, Chiron SpA, Siena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pagliaccia
authors.forename: X M
authors.initials: XM
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Tardy
authors.forename: J L
authors.initials: JL
authors.lastname: Telford
authors.forename: J M
authors.initials: JM
authors.lastname: Ruysschaert
authors.forename: V
authors.initials: V
authors.lastname: Cabiaux
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D003903:Deuterium / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D016480:Helicobacter pylori / Q000737:chemistry*; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001426:Bacterial Proteins; D005452:Fluoresceins; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; C074689:VacA protein, Helicobacter pylori; C024990:asolectin; D006859:Hydrogen; D003903:Deuterium; C007740:fluorexon