Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper.
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.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Ulrich
U
Schwarz-Linek
Jörn M
JM
Werner
Andrew R
AR
Pickford
Sivashankarappa
S
Gurusiddappa
Jung Hwa
JH
Kim
Ewa S
ES
Pilka
John A G
JA
Briggs
T Sebastian
TS
Gough
Magnus
M
Höök
Iain D
ID
Campbell
Jennifer R
JR
Potts
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001665:Binding Sites; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000378:metabolism* / Q000472:pathogenicity; D013297:Streptococcus pyogenes / Q000737:chemistry* / Q000378:metabolism* / Q000472:pathogenicity
D005353:Fibronectins