title: Distinct roles of the N-terminal and C-terminal precursor domains in the biogenesis of the Bordetella pertussis filamentous hemagglutinin.
abstract: The 220-kDa Bordetella pertussis filamentous hemagglutinin (FHA) is the major exported protein found in culture supernatants. The structural gene of FHA has a coding potential for a 367-kDa protein, and the mature form constitutes the N-terminal 60% of the 367-kDa precursor. The C-terminal domain of the precursor was found to be important for the high-level secretion of full-length FHA but not of truncated analogs (80 kDa or less). The secretion of full-length and truncated FHA polypeptides requires the presence of the approximately 100-amino-acid N-terminal domain and the outer membrane protein FhaC, homologous to the N-terminal domains of the Serratia marcescens and Proteus mirabilis hemolysins and their accessory proteins, respectively. By analogy to these hemolysins, it is likely that the N-terminal domain of the FHA precursor interacts, directly or indirectly, with the accessory protein during FHA biogenesis. However, immunogenicity and antigenicity studies suggest that the N-terminal domain of FHA is masked by its C-terminal domain and therefore should not be available for its interactions with FhaC. These observations suggest a model in which the C-terminal domain of the FHA precursor may play a role as an intramolecular chaperone to prevent premature folding of the protein. Both heparin binding and hemagglutination are expressed by the N-terminal half of FHA, indicating that this domain contains important functional regions of the molecule.
authors.affiliation: Centre d'Immunologie et de Biologie Parasitaire, INSERM 167, Institut Pasteur, Lille, France.
authors.forename: G
authors.initials: G
authors.lastname: Renauld-Mongénie
authors.forename: J
authors.initials: J
authors.lastname: Cornette
authors.forename: N
authors.initials: N
authors.lastname: Mielcarek
authors.forename: F D
authors.initials: FD
authors.lastname: Menozzi
authors.forename: C
authors.initials: C
authors.lastname: Locht
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D001886:Bordetella pertussis / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006386:Hemagglutination Tests; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D010566:Virulence Factors, Bordetella
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D006388:Hemagglutinins; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; C098052:fhaC protein, Bordetella pertussis; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis