Schwarz-Linek, U., Werner, J.M., Pickford, A.R., Gurusiddappa, S., Kim, J.H., Pilka, E.S., Briggs, J.A.G., Gough, T.S., Hook, M., Campbell, I.D. and Potts, J.R. (2003) Pathogenic bacteria attach to human fibronectin through a tandem ß-zipper. Nature, 423 (6936). pp. 177-181. ISSN 0028-0836
Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells1, 2. Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats3 in an unfolded4, 5 region of the protein. The bacterium-binding site in the amino-terminal domain (1–5F1) of Fn contains five sequential Fn type 1 (F1) modules. Here we show the structure of a streptococcal (S. dysgalactiae) FnBP peptide (B3)6, 7 in complex with the module pair 1F12F1. This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel beta-strands on sequential F1 modules—the first example of a tandem beta-zipper. Sequence analyses of larger regions of FnBPs from S. pyogenes and S. aureus reveal a repeating pattern of F1-binding motifs that match the pattern of F1 modules in 1–5F1 of Fn. In the process of Fn-mediated invasion of host cells, therefore, the bacterial proteins seem to exploit the modular structure of Fn by forming extended tandem beta-zippers. This work is a vital step forward in explaining the full mechanism of the integrin-dependent2, 8 FnBP-mediated invasion of host cells.
|Institution:||The University of York|
|Academic Units:||The University of York > Biology (York)|
|Depositing User:||York RAE Import|
|Date Deposited:||09 Feb 2009 10:06|
|Last Modified:||09 Feb 2009 10:19|
|Publisher:||Nature Publishing Group|