Abstract
Like many bacterial pathogens, Salmonella spp. use a type III secretion system to inject virulence proteins into host cells. The Salmonella invasion protein A (SipA) binds host actin, enhances its polymerization near adherent extracellular bacteria, and contributes to cytoskeletal rearrangements that internalize the pathogen. By combining x-ray crystallography of SipA with electron microscopy and image analysis of SipA-actin filaments, we show that SipA functions as a "molecular staple," in which a globular domain and two nonglobular "arms" mechanically stabilize the filament by tethering actin subunits in opposing strands. Deletion analysis of the tethering arms provides strong support for this model.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / metabolism
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Actins / metabolism*
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Binding Sites
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Crystallography, X-Ray
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Image Processing, Computer-Assisted
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Microfilament Proteins / chemistry*
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Microscopy, Electron
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Models, Molecular
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Protein Binding
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Protein Conformation
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Protein Folding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Salmonella typhimurium / chemistry
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Salmonella typhimurium / metabolism*
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Sequence Deletion
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Subtilisin / metabolism
Substances
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Actins
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Bacterial Proteins
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Microfilament Proteins
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Recombinant Proteins
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SipA protein, Salmonella
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Subtilisin