Abstract
Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ligand bound and in complex with a heparin analog called sucrose octasulfate. We identified multiple adhesion targets, including laminin and heparin, and showed that a 40 kDa domain of laminin called LG4-5 specifically binds to Ail. We also evaluated the contribution of laminin to delivery of Yops to HEp-2 cells. This work constitutes a structural description of how a bacterial outer membrane protein uses a multivalent approach to bind host cells.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Bacterial Adhesion*
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Bacterial Outer Membrane Proteins / chemistry*
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Bacterial Outer Membrane Proteins / metabolism
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Bacterial Outer Membrane Proteins / physiology
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Bacterial Proteins / metabolism
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Cell Line
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Crystallography, X-Ray
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Extracellular Matrix / metabolism
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Extracellular Matrix Proteins / metabolism
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Host-Pathogen Interactions
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Humans
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Laminin / metabolism
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Membrane Proteins / metabolism
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Molecular Chaperones / metabolism
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Molecular Sequence Data
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Protein Binding
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Protein Structure, Tertiary
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Sequence Alignment
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Sucrose / analogs & derivatives*
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Sucrose / chemistry
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Surface Properties
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Virulence Factors / chemistry*
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Virulence Factors / metabolism
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Virulence Factors / physiology
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Yersinia pestis*
Substances
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Ail protein, Yersinia pestis
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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Extracellular Matrix Proteins
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Laminin
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Membrane Proteins
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Molecular Chaperones
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Virulence Factors
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YscG protein, Yersinia
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Sucrose
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sucrose octasulfate