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

J.M. Werner; J.A.G. Briggs; T.S. Gough; M. Hook; J.R. Potts; U. Schwarz-Linek; A.R. Pickford; S. Gurusiddappa; J.H. Kim; E.S. Pilka; I.D. Campbell

doi:10.1038/nature01589

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

J.M. Werner, J.A.G. Briggs, T.S. Gough, M. Hook, J.R. Potts, U. Schwarz-Linek, A.R. Pickford, S. Gurusiddappa, J.H. Kim, E.S. Pilka, I.D. Campbell

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	177-81
Number of pages	5
Journal	Nature
Volume	423
Issue number	6936
DOIs	https://doi.org/10.1038/nature01589
Publication status	Published - 8 May 2003

Keywords

Amino Acid Motifs
Amino Acid Sequence
Bacterial Adhesion
Binding Sites
Fibronectins
Humans
Models, Molecular
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Structure, Secondary
Staphylococcus aureus
Streptococcus pyogenes

Access to Document

10.1038/nature01589

http://dx.doi.org/10.1038/nature01589

Cite this

@article{a09bc3710e014cdabbd902a233d9d140,

title = "Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper",

abstract = "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.",

keywords = "Amino Acid Motifs, Amino Acid Sequence, Bacterial Adhesion, Binding Sites, Fibronectins, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Structure, Secondary, Staphylococcus aureus, Streptococcus pyogenes",

author = "J.M. Werner and J.A.G. Briggs and T.S. Gough and M. Hook and J.R. Potts and U. Schwarz-Linek and A.R. Pickford and S. Gurusiddappa and J.H. Kim and E.S. Pilka and I.D. Campbell",

year = "2003",

month = may,

day = "8",

doi = "10.1038/nature01589",

language = "English",

volume = "423",

pages = "177--81",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "6936",

}

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

SN - 0028-0836

VL - 423

SP - 177

EP - 181

JO - Nature

JF - Nature

IS - 6936

ER -