Ail Protein Binds Ninth Type III Fibronectin Repeat ((FNIII)-F-9) within Central 120-kDa Region of Fibronectin to Facilitate Cell Binding by Yersinia pestis

作者：Tsang Tiffany M; Annis Douglas S; Kronshage Malte; Fenno Jesse T; Usselman Lisa D; Mosher Deane F; Krukonis Eric S^*

来源：Journal of Biological Chemistry, 2012, 287(20): 16759-16767.

DOI：10.1074/jbc.M112.358978

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.

• 出版日期2012-5-11