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    Visualization of the type III secretion sorting platform of Shigella flexneri

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    Hu_2015_NAS.pdf (4.093Mb)
    Issue Date
    2015-01-27
    Author
    Hu, Bo
    Morado, Dustin R.
    Margolin, William
    Rohde, John R.
    Arizmendi Perez, Olivia
    Picking, Wendy Lynn
    Picking, William D.
    Liu, Jun
    Publisher
    National Academy of Sciences
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    Bacterial 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.
    URI
    http://hdl.handle.net/1808/22200
    DOI
    https://doi.org/10.1073/pnas.1411610112
    Collections
    • Pharmaceutical Chemistry Scholarly Works [343]
    Citation
    Hu, 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.1411610112

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    KU Libraries
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    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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