Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.

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 essent...

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Autores principales:	Grazyna Domańska, Christian Motz, Michael Meinecke, Anke Harsman, Panagiotis Papatheodorou, Boris Reljic, Elke A Dian-Lothrop, Antoine Galmiche, Oliver Kepp, Lars Becker, Kathrin Günnewig, Richard Wagner, Joachim Rassow
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a4b5be66caac4e40b235c363349940c3
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spelling	oai:doaj.org-article:a4b5be66caac4e40b235c363349940c32021-12-02T20:00:44ZHelicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.1553-73661553-737410.1371/journal.ppat.1000878https://doaj.org/article/a4b5be66caac4e40b235c363349940c32010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20442789/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.Grazyna DomańskaChristian MotzMichael MeineckeAnke HarsmanPanagiotis PapatheodorouBoris ReljicElke A Dian-LothropAntoine GalmicheOliver KeppLars BeckerKathrin GünnewigRichard WagnerJoachim RassowPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 4, p e1000878 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Grazyna Domańska Christian Motz Michael Meinecke Anke Harsman Panagiotis Papatheodorou Boris Reljic Elke A Dian-Lothrop Antoine Galmiche Oliver Kepp Lars Becker Kathrin Günnewig Richard Wagner Joachim Rassow Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
description	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.
format	article
author	Grazyna Domańska Christian Motz Michael Meinecke Anke Harsman Panagiotis Papatheodorou Boris Reljic Elke A Dian-Lothrop Antoine Galmiche Oliver Kepp Lars Becker Kathrin Günnewig Richard Wagner Joachim Rassow
author_facet	Grazyna Domańska Christian Motz Michael Meinecke Anke Harsman Panagiotis Papatheodorou Boris Reljic Elke A Dian-Lothrop Antoine Galmiche Oliver Kepp Lars Becker Kathrin Günnewig Richard Wagner Joachim Rassow
author_sort	Grazyna Domańska
title	Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
title_short	Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
title_full	Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
title_fullStr	Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
title_full_unstemmed	Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
title_sort	helicobacter pylori vaca toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/a4b5be66caac4e40b235c363349940c3
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Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.

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