Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.

The type III secretion system (T3SS) is a complex macromolecular machinery employed by a number of Gram-negative pathogens to inject effectors directly into the cytoplasm of eukaryotic cells. ExoU from the opportunistic pathogen Pseudomonas aeruginosa is one of the most aggressive toxins injected by...

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Autores principales:	Claire Gendrin, Carlos Contreras-Martel, Stéphanie Bouillot, Sylvie Elsen, David Lemaire, Dimitrios A Skoufias, Philippe Huber, Ina Attree, Andréa Dessen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/106857155d6e4cb5ae11921c3aea2542
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spelling	oai:doaj.org-article:106857155d6e4cb5ae11921c3aea25422021-11-18T06:04:33ZStructural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.1553-73661553-737410.1371/journal.ppat.1002637https://doaj.org/article/106857155d6e4cb5ae11921c3aea25422012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496657/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The type III secretion system (T3SS) is a complex macromolecular machinery employed by a number of Gram-negative pathogens to inject effectors directly into the cytoplasm of eukaryotic cells. ExoU from the opportunistic pathogen Pseudomonas aeruginosa is one of the most aggressive toxins injected by a T3SS, leading to rapid cell necrosis. Here we report the crystal structure of ExoU in complex with its chaperone, SpcU. ExoU folds into membrane-binding, bridging, and phospholipase domains. SpcU maintains the N-terminus of ExoU in an unfolded state, required for secretion. The phospholipase domain carries an embedded catalytic site whose position within ExoU does not permit direct interaction with the bilayer, which suggests that ExoU must undergo a conformational rearrangement in order to access lipids within the target membrane. The bridging domain connects catalytic domain and membrane-binding domains, the latter of which displays specificity to PI(4,5)P₂. Both transfection experiments and infection of eukaryotic cells with ExoU-secreting bacteria show that ExoU ubiquitination results in its co-localization with endosomal markers. This could reflect an attempt of the infected cell to target ExoU for degradation in order to protect itself from its aggressive cytotoxic action.Claire GendrinCarlos Contreras-MartelStéphanie BouillotSylvie ElsenDavid LemaireDimitrios A SkoufiasPhilippe HuberIna AttreeAndréa DessenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 4, p e1002637 (2012)
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 Claire Gendrin Carlos Contreras-Martel Stéphanie Bouillot Sylvie Elsen David Lemaire Dimitrios A Skoufias Philippe Huber Ina Attree Andréa Dessen Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.
description	The type III secretion system (T3SS) is a complex macromolecular machinery employed by a number of Gram-negative pathogens to inject effectors directly into the cytoplasm of eukaryotic cells. ExoU from the opportunistic pathogen Pseudomonas aeruginosa is one of the most aggressive toxins injected by a T3SS, leading to rapid cell necrosis. Here we report the crystal structure of ExoU in complex with its chaperone, SpcU. ExoU folds into membrane-binding, bridging, and phospholipase domains. SpcU maintains the N-terminus of ExoU in an unfolded state, required for secretion. The phospholipase domain carries an embedded catalytic site whose position within ExoU does not permit direct interaction with the bilayer, which suggests that ExoU must undergo a conformational rearrangement in order to access lipids within the target membrane. The bridging domain connects catalytic domain and membrane-binding domains, the latter of which displays specificity to PI(4,5)P₂. Both transfection experiments and infection of eukaryotic cells with ExoU-secreting bacteria show that ExoU ubiquitination results in its co-localization with endosomal markers. This could reflect an attempt of the infected cell to target ExoU for degradation in order to protect itself from its aggressive cytotoxic action.
format	article
author	Claire Gendrin Carlos Contreras-Martel Stéphanie Bouillot Sylvie Elsen David Lemaire Dimitrios A Skoufias Philippe Huber Ina Attree Andréa Dessen
author_facet	Claire Gendrin Carlos Contreras-Martel Stéphanie Bouillot Sylvie Elsen David Lemaire Dimitrios A Skoufias Philippe Huber Ina Attree Andréa Dessen
author_sort	Claire Gendrin
title	Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.
title_short	Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.
title_full	Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.
title_fullStr	Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.
title_full_unstemmed	Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.
title_sort	structural basis of cytotoxicity mediated by the type iii secretion toxin exou from pseudomonas aeruginosa.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/106857155d6e4cb5ae11921c3aea2542
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Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa.

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