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

TY - JOUR

T1 - Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper

AU - Werner, J.M.

AU - Briggs, J.A.G.

AU - Gough, T.S.

AU - Hook, M.

AU - Potts, J.R.

AU - Schwarz-Linek, U.

AU - Pickford, A.R.

AU - Gurusiddappa, S.

AU - Kim, J.H.

AU - Pilka, E.S.

AU - Campbell, I.D.

PY - 2003/5/8

Y1 - 2003/5/8

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Bacterial Adhesion

KW - Binding Sites

KW - Fibronectins

KW - Humans

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Nuclear Magnetic Resonance, Biomolecular

KW - Protein Binding

KW - Protein Structure, Secondary

KW - Staphylococcus aureus

KW - Streptococcus pyogenes

U2 - 10.1038/nature01589

DO - 10.1038/nature01589

M3 - Article

C2 - 12736686

VL - 423

SP - 177

EP - 181

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6936

ER -