Membrane topology of VacA cytotoxin from H. pylori.
The interaction of VacA with membranes involves: (i) a low pH activation that induces VacA monomerization in solution, (ii) binding of the monomers to the membrane, (iii) oligomerization and (iv) channel formation. To better understand the structure-activity relationship of VacA, we determined its topology in a lipid membrane by a combination of proteolytic, structural and fluorescence techniques. Residues 40-66, 111-169, 205-266, 548-574 and 723-767 were protected from proteolysis because of their interaction with the membrane. This last peptide was shown to most probably adopt a surface orientation. Both alpha-helices and beta-sheets were found in the structure of the protected peptides.
Wang
X
X
Structure et Fonction des Membranes Biologiques, CP 20612, Université Libre de Bruxelles, Boulevard du Triomphe, B-1050 Brussels, Belgium.
Wattiez
R
R
Paggliacia
C
C
Telford
J L
JL
Ruysschaert
J
J
Cabiaux
V
V
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D016480:Helicobacter pylori / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000378:metabolism; D012995:Solubility; D013055:Spectrophotometry, Infrared
D001426:Bacterial Proteins; D008081:Liposomes; D010446:Peptide Fragments; D011510:Proteolipids; C074689:VacA protein, Helicobacter pylori; C020485:proteoliposomes