Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper

J.M. Werner, J.A.G. Briggs, T.S. Gough, M. Hook, J.R. Potts, U. Schwarz-Linek, A.R. Pickford, S. Gurusiddappa, J.H. Kim, E.S. Pilka, I.D. Campbell

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)177-81
Number of pages5
JournalNature
Volume423
Issue number6936
DOIs
Publication statusPublished - 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

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