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

Schwarz-Linek, Ulrich, Werner, Jörn M., Pickford, Andrew R., Gurusiddappa, Sivashankarappa, Kim, Jung Hwa, Pilka, Ewa S., Briggs, John A. G., Gough, T. Sebastian, Höök, Magnus, Campbell, Iain D. and Potts, Jennifer R. (2003) Letter to Nature. Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper Nature, 423, (6936), pp. 177-181. (doi:10.1038/nature01589).


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Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells1, 2. Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats3 in an unfolded4, 5 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)6, 7 in complex with the module pair 1F12F1. This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel -strands on sequential F1 modules—the first example of a tandem -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 -zippers. This work is a vital step forward in explaining the full mechanism of the integrin-dependent2, 8 FnBP-mediated invasion of host cells.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1038/nature01589
ISSNs: 0028-0836 (print)
Related URLs:
Keywords: fibronectin, staphylococcus aureus, streptococcus pyogenes, structure, function, adhesion, NMR
ePrint ID: 40778
Date :
Date Event
20 December 2002Submitted
8 May 2003Published
Date Deposited: 10 Jul 2006
Last Modified: 16 Apr 2017 21:51
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/40778

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