Abstract:
Many pathogenic and commensal bacteria express pili, long hair-like protein polymers that enable adhesion to host tissues. The pili of Gram-positive bacteria are unique as they are assembled by specialised transpeptidases (sortases) through covalent linkages. In the common human pathogen Streptococcus pyogenes, the major pilin FctA forms the polymeric pilus fibre, while the minor pilin Cpa is the adhesin found at the pilus tip. The pilus is anchored to the streptococcal cell wall through the basal pilin FctB. Here, we present the crystal structure of FctB at 1.9 Å resolution. It reveals an immunoglobulin (Ig)-like N-terminal domain with an extended proline-rich tail. Surprisingly, the Ig-like domain is structurally homologous to the N-terminal domain of the major pilin FctA. This led to the identification of a conserved lysine residue as the putative site of covalent linkage to the pilus assembly, which we confirmed by mass spectrometry analysis of complete S. pyogenes pili. The C-terminal tail FA1-MS12 Infection and Disease 26th European Crystallographic Meeting, ECM 26, Darmstadt, 2010 Acta Cryst. (2010). A66, Page s34 s34 forms a polyproline-II-like helix that seems to be a common feature of many Gram-positive cell-wall anchored virulence factors, and particularly of basal pilins. Together, we identified structural characteristics of pilins that direct their incorporation into the pilus polymer.
