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A highly unusual thioester bond in a pilus adhesin is required for efficient host cell interaction
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Pointon, Jonathan A., Smith, Wendy D., Saalbach, Gerhard, Crow, Allister, Kehoe, Michael A. and Banfield, Mark J. (2010) A highly unusual thioester bond in a pilus adhesin is required for efficient host cell interaction. Journal of Biological Chemistry, 285 (44). pp. 33858-33866. doi:10.1074/jbc.M110.149385 ISSN 0021-9258.
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Official URL: http://dx.doi.org/10.1074/jbc.M110.149385
Abstract
Many bacterial pathogens present adhesins at the tips of long macromolecular filaments known as pili that are often important virulence determinants. Very little is known about how pili presented by Gram-positive pathogens mediate host cell binding. The crystal structure of a pilus adhesin from the important human pathogen Streptococcus pyogenes reveals an internal thioester bond formed between the side chains of a cysteine and a glutamine residue. The presence of the thioester was verified using UV-visible spectroscopy and mass spectrometry. This unusual bond has only previously been observed in thioester domains of complement and complement-like proteins where it is used to form covalent attachment to target molecules. The structure also reveals two intramolecular isopeptide bonds, one of these formed through a Lys/Asp residue pair, which are strategically positioned to confer protein stability. Removal of the internal thioester by allele-replacement mutagenesis in S. pyogenes severely compromises bacterial adhesion to model host cells. Although current paradigms of bacterial/host cell interaction envisage strong non-covalent interactions, the present study suggests cell adhesion could also involve covalent bonds.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
| Journal or Publication Title: | Journal of Biological Chemistry | ||||||
| Publisher: | American Society for Biochemistry and Molecular Biology | ||||||
| ISSN: | 0021-9258 | ||||||
| Official Date: | 29 October 2010 | ||||||
| Dates: |
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| Volume: | 285 | ||||||
| Number: | 44 | ||||||
| Page Range: | pp. 33858-33866 | ||||||
| DOI: | 10.1074/jbc.M110.149385 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access |
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