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

Ulrich Schwarz-Linek, Jörn M. Werner, Andrew R. Pickford, Sivashankarappa Gurusiddappa, Jung H. Kim, Ewa S. Pilka, John A. G. Briggs, T. Sebastian Gough, Magnus Höök, Iain D. Campbell, Jennifer R. Potts

Research output: Contribution to journalArticlepeer-review

318 Citations (Scopus)

Abstract

Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells(1,2). Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats(3) in an unfolded(4,5) region of the protein. The bacterium-binding site in the amino-terminal domain ((1-5)F1) 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 (1)F1(2)F1. This identifies (1)F1-and (2)F1-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 (1-5)F1 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(2,8) FnBP-mediated invasion of host cells.

Original languageEnglish
Pages (from-to)177-181
Number of pages5
JournalNature
Volume423
Issue number6936
DOIs
Publication statusPublished - 8 May 2003

Keywords

  • F1 MODULE PAIR
  • STAPHYLOCOCCUS-AUREUS
  • BINDING-PROTEIN
  • STREPTOCOCCUS-PYOGENES
  • NMR-SPECTROSCOPY
  • EPITHELIAL-CELLS
  • CHEMICAL-SHIFT
  • LIGAND-BINDING
  • ADHERENCE
  • SEQUENCE

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