Helicobacter pylori VacA Toxin/Subunit p34: Targeting of an Anion Channel to the Inner Mitochondrial Membrane
DC Element | Wert | Sprache |
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dc.contributor.author | Domanska, Grazyna | |
dc.contributor.author | Motz, Christian | |
dc.contributor.author | Meinecke, Michael | |
dc.contributor.author | Harsman, Anke | |
dc.contributor.author | Papatheodorou, Panagiotis | |
dc.contributor.author | Reljic, Boris | |
dc.contributor.author | Dian-Lothrop, Elke A. | |
dc.contributor.author | Galmiche, Antoine | |
dc.contributor.author | Kepp, Oliver | |
dc.contributor.author | Becker, Lars | |
dc.contributor.author | Guennewig, Kathrin | |
dc.contributor.author | Wagner, Richard | |
dc.contributor.author | Rassow, Joachim | |
dc.date.accessioned | 2021-12-23T16:23:03Z | - |
dc.date.available | 2021-12-23T16:23:03Z | - |
dc.date.issued | 2010 | |
dc.identifier.issn | 15537366 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14399 | - |
dc.description.abstract | The vacuolating toxin VacA, released by 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. | |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [SPP1131, SFB 388, SFB 431]; Landesgraduiertenstipendium des Landes Baden-Wuerttemberg; Funding: This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG, http://www.dfg.de; Schwerpunktprogramm SPP1131 and Sonderforschungsbereiche SFB 388 and SFB 431) and by a Landesgraduiertenstipendium des Landes Baden-Wuerttemberg for EADL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
dc.language.iso | en | |
dc.publisher | PUBLIC LIBRARY SCIENCE | |
dc.relation.ispartof | PLOS PATHOGENS | |
dc.subject | BETA-BARREL | |
dc.subject | CYTOCHROME-C RELEASE | |
dc.subject | GASTRIC-CANCER CELLS | |
dc.subject | IMPORT PORE | |
dc.subject | LIPID-BILAYERS | |
dc.subject | Microbiology | |
dc.subject | Parasitology | |
dc.subject | PREPROTEIN TRANSLOCASE | |
dc.subject | SACCHAROMYCES-CEREVISIAE | |
dc.subject | SELECTIVE CHANNELS | |
dc.subject | TOM40 FORMS | |
dc.subject | VACUOLATING CYTOTOXIN | |
dc.subject | Virology | |
dc.title | Helicobacter pylori VacA Toxin/Subunit p34: Targeting of an Anion Channel to the Inner Mitochondrial Membrane | |
dc.type | journal article | |
dc.identifier.doi | 10.1371/journal.ppat.1000878 | |
dc.identifier.isi | ISI:000277722400048 | |
dc.description.volume | 6 | |
dc.description.issue | 4 | |
dc.contributor.orcid | 0000-0003-1414-6951 | |
dc.contributor.orcid | 0000-0002-6081-9558 | |
dc.contributor.orcid | 0000-0003-3571-695X | |
dc.contributor.researcherid | N-7509-2015 | |
dc.contributor.researcherid | C-4833-2013 | |
dc.contributor.researcherid | N-2763-2017 | |
dc.identifier.eissn | 15537374 | |
dc.publisher.place | 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA | |
dcterms.isPartOf.abbreviation | PLoS Pathog. | |
dcterms.oaStatus | Green Published, Green Submitted, gold | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | WaRi703 | - |
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geprüft am 08.06.2024