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A Highly Unusual Thioester Bond in a Pilus Adhesin Is Required for Efficient Host Cell Interaction

Lookup NU author(s): Jonathan Pointon, Dr Wendy Smith, Dr Mark Banfield

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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.


Publication metadata

Author(s): Pointon JA, Smith WD, Saalbach G, Crow A, Kehoe MA, Banfield MJ

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2010

Volume: 285

Issue: 44

Pages: 33858-33866

Print publication date: 01/10/2010

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology

URL: http://dx.doi.org/10.1074/jbc.M110.149385

DOI: 10.1074/jbc.M110.149385


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Funding

Funder referenceFunder name
Royal Society
G0400849Medical Research Council (United Kingdom)
G0600309Medical Research Council (United Kingdom)

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