Beta-helix model for the filamentous haemagglutinin adhesin of Bordetella pertussis and related bacterial secretory proteins

Bordetella pertussis establishes infection by attaching to epithelial cells of the respiratory tract. One of its adhesins is filamentous haemagglutini n (FHA), a 500-Angstrom -long secreted protein that is rich in beta -struct ure and contains two regions, R1 and R2, of tandem 19-residue repeats. Two models have been proposed in which the central shaft is (i) a hairpin made up of a pairing of two long antiparallel beta -sheets; or (ii) a beta -heli x in which the polypeptide chain is coiled to form three long parallel beta -sheets. We have analysed a truncated variant of FHA by electron microscop y (negative staining, shadowing and scanning transmission electron microsco py of unstained specimens): these observations support the latter model. Fu rther support comes from detailed sequence analysis and molecular modelling studies. We applied a profile search method to the sequences adjacent to a nd between R1 and R2 and found additional 'covert' copies of the same motif s that may be recognized in overt form in the R1 and R2 sequence repeats. T heir total number is sufficient to support the tenet of the beta -helix mod el that the shaft domain - a 350 Angstrom rod - should consist of a continu ous run of these motifs, apart from loop inserts. The N-terminus, which doe s not contain such repeats, was found to be weakly homologous to cyclodextr in transferase, a protein of known immunoglobulin-like structure. Drawing o n crystal structures of known beta -helical proteins, we developed structur al models of the coil motifs putatively formed by the R1 and R2 repeats. Fi nally, we applied the same profile search method to the sequence database a nd found several other proteins - all large secreted proteins of bacterial provenance - that have similar repeats and probably also similar structures .