期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 20, 页码 16759-16767出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.358978
关键词
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资金
- National Institutes of Health through NHLBI [R01HL021644]
- National Institutes of Health through NIAID [R21AI090194, R03AI092318]
- Office of the Vice President of Research (OVPR) at the University of Michigan
- Department of Microbiology and Immunology at the University of Michigan
The Yersinia pestis adhesin molecule Ail interacts with the extracellular matrix protein fibronectin (Fn) on host cells to facilitate efficient delivery of cytotoxic Yop proteins, a process essential for plague virulence. A number of bacterial pathogens are known to bind to the N-terminal region of Fn, comprising type I Fn (FNI) repeats. Using proteolytically generated Fn fragments and purified recombinant Fn fragments, we demonstrated that Ail binds the centrally located 120-kDa fragment containing type III Fn (FNIII) repeats. A panel of monoclonal antibodies (mAbs) that recognize specific epitopes within the 120-kDa fragment demonstrated that mAb binding to (FNIII)-F-9 blocks Ail-mediated bacterial binding to Fn. Epitopes of three mAbs that blocked Ail binding to Fn were mapped to a similar face of (FNIII)-F-9. Antibodies directed against (FNIII)-F-9 also inhibited Ail-dependent cell binding activity, thus demonstrating the biological relevance of this Ail binding region on Fn. Bacteria expressing Ail on their surface could also bind a minimal fragment of Fn containing repeats 9-10FNIII, and this binding was blocked by a mAb specific for 9FNIII. These data demonstrate that Ail binds to (FNIII)-F-9 of Fn and presents Fn to host cells to facilitate cell binding and delivery of Yops (cytotoxins of Y. pestis), a novel interaction, distinct from other bacterial Fn-binding proteins.
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