Membrane topology of VacA cytotoxin from H-pylori

The interaction of VacA with membranes involves: (i) a low pH activation th at 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 t opology 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 orie ntation. Both alpha-helices and beta-sheets were found in the structure of the protected peptides, (C) 2000 Federation of European Biochemical Societi es. Published by Elsevier Science B.V. All rights reserved.