Membrane channel structure of Helicobacter pylori vacuolating toxin: role of multiple GXXXG motifs in cylindrical channels

Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5988-91. doi: 10.1073/pnas.0308694101. Epub 2004 Apr 5.


Helicobacter pylori is a human pathogen responsible for severe gastric diseases such as peptic ulcers, gastric adenocarcinoma, and gastric lymphoma. Vacuolating toxin (VacA) is crucial in facilitating the colonization of the gastric lining by inducing cell apoptosis and immune suppression. VacA inserts into membranes and forms a hexameric, anion-selective pore. Here we present a structural model of the VacA pore that strongly resembles the structure of an unrelated anion-selective channel, MscS. In our model, Gly residues in GXXXG motifs pack against small Ala or Val side chains to generate the pore. Our model suggests that the same design of two anion-selective channels was achieved by two different evolutionary paths and provides insight into the mechanism of VacA function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Helicobacter pylori / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation


  • Bacterial Proteins
  • VacA protein, Helicobacter pylori

Associated data

  • PDB/1SEW