ABSTRACT
The invasin protein encoded by enteropathogenic Yersinia allows entry of bacteria into intestinal M cells by binding to integrin receptors. In cultured cells, invasin-mediated uptake requires proteins involved in endocytosis and signaling to the cell cytoskeleton. At least four different factors have been demonstrated to play a role in regulating the efficiency of invasin-promoted uptake. These include receptor-ligand affinity, receptor clustering, signaling through focal adhesion kinase, and stimulation of cytoskeletal rearrangements by small GTP binding proteins.
Subject(s)
Adhesins, Bacterial , Bacterial Proteins/metabolism , Integrins/metabolism , Yersinia/pathogenicity , Animals , Bacterial Adhesion , Bacterial Proteins/chemistry , Cytoskeleton/metabolism , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , GTP-Binding Proteins/metabolism , Humans , Integrins/chemistry , Protein-Tyrosine Kinases/metabolism , Signal Transduction , Yersinia/chemistry , Yersinia/physiologyABSTRACT
The Yersinia pseudotuberculosis invasin protein promotes bacterial entry by binding to host cell integrins with higher affinity than natural substrates such as fibronectin. The 2.3 angstrom crystal structure of the invasin extracellular region reveals five domains that form a 180 angstrom rod with structural similarities to tandem fibronectin type III domains. The integrin-binding surfaces of invasin and fibronectin include similarly located key residues, but in the context of different folds and surface shapes. The structures of invasin and fibronectin provide an example of convergent evolution, in which invasin presents an optimized surface for integrin binding, in comparison with host substrates.
