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dc.contributor.authorLi, Mo
dc.contributor.authorLe Trong, Isolde
dc.contributor.authorCarl, Mike A.
dc.contributor.authorLarson, Eric T.
dc.contributor.authorChou, Seemay
dc.contributor.authorDe Leon, Justin A.
dc.contributor.authorDove, Simon L.
dc.contributor.authorStenkamp, Ronald E.
dc.contributor.authorMougous, Joseph D.
dc.date.accessioned2012-12-21T18:42:26Z
dc.date.issued2012
dc.identifier.citationLi, Mo, Isolde Le Trong, Mike A. Carl, Eric T. Larson, Seemay Chou, Justin A. De Leon, Simon L. Dove, Ronald E. Stenkamp, and Joseph D. Mougous. 2012. Structural basis for type VI secretion effector recognition by a cognate immunity protein. PLoS Pathogens 8(4): e1002613.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10121033
dc.description.abstractThe type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three effector proteins, \(\underline t\)ype VI \(\underline s\)ecretion \(\underline e\)xported 1–3 (Tse1–3), to recipient Gram-negative cells. The Tse2 protein is a cytoplasmic effector that acts as a potent inhibitor of target cell proliferation, thus providing a pronounced fitness advantage for P. aeruginosa donor cells. P. aeruginosa utilizes a dedicated immunity protein, \(\underline t\)ype VI \(\underline s\)ecretion \(\underline i\)mmunity 2 (Tsi2), to protect against endogenous and intercellularly-transferred Tse2. Here we show that Tse2 delivered by the T6SS efficiently induces quiescence, not death, within recipient cells. We demonstrate that despite direct interaction of Tsi2 and Tse2 in the cytoplasm, Tsi2 is dispensable for targeting the toxin to the secretory apparatus. To gain insights into the molecular basis of Tse2 immunity, we solved the 1.00 \(\mathring A \) X-ray crystal structure of Tsi2. The structure shows that Tsi2 assembles as a dimer that does not resemble previously characterized immunity or antitoxin proteins. A genetic screen for Tsi2 mutants deficient in Tse2 interaction revealed an acidic patch distal to the Tsi2 homodimer interface that mediates toxin interaction and immunity. Consistent with this finding, we observed that destabilization of the Tsi2 dimer does not impact Tse2 interaction. The molecular insights into Tsi2 structure and function garnered from this study shed light on the mechanisms of T6 effector secretion, and indicate that the Tse2–Tsi2 effector–immunity pair has features distinguishing it from previously characterized toxin–immunity and toxin–antitoxin systems.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1002613en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325213/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectbiochemistryen_US
dc.subjectproteinsen_US
dc.subjectchaperone proteinsen_US
dc.subjectprotein interactionsen_US
dc.subjectprotein structureen_US
dc.subjectmicrobiologyen_US
dc.subjectbacterial pathogensen_US
dc.subjectgram negativeen_US
dc.subjectmicrobial ecologyen_US
dc.subjectmicrobial evolutionen_US
dc.subjectmicrobial pathogensen_US
dc.titleStructural Basis for Type VI Secretion Effector Recognition by a Cognate Immunity Proteinen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorDove, Simon L.
dc.date.available2012-12-21T18:42:26Z
dc.identifier.doi10.1371/journal.ppat.1002613*
dash.contributor.affiliatedDove, Simon


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