Membrane channel structure of Helicobacter pylori vacuolating toxin: Role of multiple GXXXG motifs in cylindrical channels
- Department of Chemistry and Biochemistry, University of California Los Angeles–Department of Energy Center for Genomics and Proteomics, Molecular Biology Institute, Boyer Hall, University of California, Los Angeles, CA 90095-1570
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Edited by William F. DeGrado, University of Pennsylvania School of Medicine, Philadelphia, PA, and approved March 1, 2004 (received for review December 29, 2003)
Abstract
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.
Footnotes
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↵ * To whom correspondence should be addressed. E-mail: bowie{at}mbi.ucla.edu.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: VacA, vacuolating toxin; TM, transmembrane; MC, Monte Carlo; rmsd, rms deviation.
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Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 1SEW).
- Copyright © 2004, The National Academy of Sciences
