Identification of two protein-binding and functional regions of curli, a surface organelle and virulence determinant of Escherichia coli.

Curli are surface organelles of Escherichia coli. These fibrous proteins, formed by polymerization of a 15-kDa subunit, are expressed by E. coli strains associated with severe infections in humans. A remarkable property of curli is their ability to interact with a wide range of human proteins, interactions that contribute to the enhanced virulence of curli-expressing E. coli. To define the protein-binding region(s) of curli, we investigated the binding properties of overlapping synthetic peptides covering the curli subunit. Two peptides, one covering a 24-amino acid residue sequence in the NH(2)-terminal half of the subunit (NNS24) and one corresponding to the 26 COOH-terminal residues (VDQ26), were found to bind a number of human proteins. Physiochemical analysis revealed that NNS24 adopts a thermally stable beta-structure, and in solution the peptide forms soluble multimers, predominantly octamers. Intact curli are known to activate the proinflammatory and procoagulant contact system, and when added to human plasma, the NNS24 and VDQ26 peptides induced the release of the potent vasoactive peptide bradykinin. The results map important curli functions to the regions corresponding to the NNS24 and VDQ26 sequences.