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dc.contributor.authorHu, Bo
dc.contributor.authorMorado, Dustin R.
dc.contributor.authorMargolin, William
dc.contributor.authorRohde, John R.
dc.contributor.authorArizmendi Perez, Olivia
dc.contributor.authorPicking, Wendy Lynn
dc.contributor.authorPicking, William D.
dc.contributor.authorLiu, Jun
dc.date.accessioned2016-12-13T17:14:19Z
dc.date.available2016-12-13T17:14:19Z
dc.date.issued2015-01-27
dc.identifier.citationHu, B., Morado, D. R., Margolin, W., Rohde, J. R., Arizmendi, O., Picking, W. L., … Liu, J. (2015). Visualization of the type III secretion sorting platform of Shigella flexneri . Proc Natl Acad Sci USA, 112(4), 1047–1052. doi:10.1073/pnas.1411610112en_US
dc.identifier.urihttp://hdl.handle.net/1808/22200
dc.description.abstractBacterial type III secretion machines are widely used to inject virulence proteins into eukaryotic host cells. These secretion machines are evolutionarily related to bacterial flagella and consist of a large cytoplasmic complex, a transmembrane basal body, and an extracellular needle. The cytoplasmic complex forms a sorting platform essential for effector selection and needle assembly, but it remains largely uncharacterized. Here we use high-throughput cryoelectron tomography (cryo-ET) to visualize intact machines in a virulent Shigella flexneri strain genetically modified to produce minicells capable of interaction with host cells. A high-resolution in situ structure of the intact machine determined by subtomogram averaging reveals the cytoplasmic sorting platform, which consists of a central hub and six spokes, with a pod-like structure at the terminus of each spoke. Molecular modeling of wild-type and mutant machines allowed us to propose a model of the sorting platform in which the hub consists mainly of a hexamer of the Spa47 ATPase, whereas the MxiN protein comprises the spokes and the Spa33 protein forms the pods. Multiple contacts among those components are essential to align the Spa47 ATPase with the central channel of the MxiA protein export gate to form a unique nanomachine. The molecular architecture of the Shigella type III secretion machine and its sorting platform provide the structural foundation for further dissecting the mechanisms underlying type III secretion and pathogenesis and also highlight the major structural distinctions from bacterial flagella.en_US
dc.publisherNational Academy of Sciencesen_US
dc.subjectNanomachineen_US
dc.subjectInjectisomeen_US
dc.subjectPathogen-Host Interactionen_US
dc.subjectCryo-Electron Tomographyen_US
dc.subjectProtein Secretionen_US
dc.titleVisualization of the type III secretion sorting platform of Shigella flexnerien_US
dc.typeArticleen_US
kusw.kuauthorPicking, Wendy L.
kusw.kuauthorPicking, William D.
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.1073/pnas.1411610112en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccess


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