Grażyna Domańska, Christian Motz, Michael Meinecke, Anke Harsman, Panagiotis Papatheodorou, Boris Reljic, Elke Andreas Dian, Antoine Galmiche, Oliver Kepp, Lars Becker, Kathrin Günnewig, Richard Wagner, Joachim Rassow
- The vacuolating toxin VacA, released by \(\textit{ Helicobacter pylori}\), is an important virulence factor in the pathogenesis of gastritis and gastroduodenal ulcers. VacA contains two subunits: The p58 subunit mediates entry into target cells, and the p34 subunit mediates targeting to mitochondria and is essential for toxicity. In this study we found that targeting to mitochondria is dependent on a unique signal sequence of 32 uncharged amino acid residues at the p34 N-terminus. Mitochondrial import of p34 is mediated by the import receptor Tom20 and the import channel of the outer membrane TOM complex, leading to insertion of p34 into the mitochondrial inner membrane. p34 assembles in homo-hexamers of extraordinary high stability. CD spectra of the purified protein indicate a content of >40% \(\beta\)-strands, similar to pore-forming \(\beta\)-barrel proteins. p34 forms an anion channel with a conductivity of about 12 pS in 1.5 M KCl buffer. Oligomerization and channel formation are independent both of the 32 uncharged N-terminal residues and of the p58 subunit of the toxin. The conductivity is efficiently blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a reagent known to inhibit VacA-mediated apoptosis. We conclude that p34 essentially acts as a small pore-forming toxin, targeted to the mitochondrial inner membrane by a special hydrophobic N-terminal signal.
MetadatenAuthor: | Grażyna DomańskaGND, Christian MotzGND, Michael MeineckeGND, Anke HarsmanGND, Panagiotis PapatheodorouGND, Boris ReljicGND, Elke Andreas DianGND, Antoine GalmicheGND, Oliver KeppGND, Lars BeckerGND, Kathrin GünnewigGND, Richard WagnerGND, Joachim RassowORCiDGND |
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URN: | urn:nbn:de:hbz:294-71558 |
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DOI: | https://doi.org/10.1371/journal.ppat.1000878 |
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Parent Title (English): | PLoS pathogens |
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Subtitle (English): | targeting of an anion channel to the inner mitochondrial membrane |
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Publisher: | Public Library of Science |
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Place of publication: | Lawrence |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2020/05/14 |
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Date of first Publication: | 2010/04/29 |
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Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
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Tag: | Cell membranes; Membrane proteins; Mitochondria; Outer membrane proteins; Proteases; Reticulocytes; Toxins; Urea |
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Volume: | 6 |
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Issue: | 4, Artikel e1000878 |
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First Page: | e1000878-1 |
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Last Page: | e1000878-14 |
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Institutes/Facilities: | Institut für Biochemie und Pathobiochemie, Abteilung Zellbiochemie |
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open_access (DINI-Set): | open_access |
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Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |
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