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A highly unusual thioester bond in a pilus adhesin is required for efficient host cell interaction.

DOI: 10.1074/jbc.M110.149385 DOI Help
PMID: 20729215 PMID Help

Authors: Jonathan Pointon (University of Newcastle) , Wendy Smith (University of Newcastle) , Gerhard Saalbach (John Innes Centre) , Allister Crow (Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich) , Michael Kehoe (Newcastle University) , Mark Banfield (John Innes Centre)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: August 2010

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.

Journal Keywords: Bacterial; Alleles; Aspartic; Cell; Crystallography; X-Ray; Escherichia; Esters; Fimbriae; Bacterial; Lysine; Mutagenesis; Peptides; Protein; Spectrophotometry; Ultraviolet; Streptococcus; Streptococcus pyogenes

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

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