Abstract
Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells. Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats in an unfolded 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) 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-dependent FnBP-mediated invasion of host cells.
Original language | English |
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Pages (from-to) | 177-81 |
Number of pages | 5 |
Journal | Nature |
Volume | 423 |
Issue number | 6936 |
DOIs | |
Publication status | Published - 8 May 2003 |
Keywords
- Amino Acid Motifs
- Amino Acid Sequence
- Bacterial Adhesion
- Binding Sites
- Fibronectins
- Humans
- Models, Molecular
- Molecular Sequence Data
- Nuclear Magnetic Resonance, Biomolecular
- Protein Binding
- Protein Structure, Secondary
- Staphylococcus aureus
- Streptococcus pyogenes