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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).

Record type: Article


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.

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Submitted date: 20 December 2002
Published date: 8 May 2003
Keywords: fibronectin, staphylococcus aureus, streptococcus pyogenes, structure, function, adhesion, NMR
Organisations: Biological Sciences


Local EPrints ID: 40778
ISSN: 0028-0836
PURE UUID: 6bd9d9ce-4e01-4618-b68d-63482652dc08
ORCID for Jörn M. Werner: ORCID iD

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Date deposited: 10 Jul 2006
Last modified: 17 Jul 2017 15:33

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

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