Bordetella pertussis binds to human C4b-binding protein (C4BP) at a site similar to that used by the natural ligand C4b.
Human complement regulators are important targets for pathogenic microorganisms. In one such interaction, Bordetella pertussis binds human C4b-binding protein (C4BP), a high-molecular-weight plasma protein that acts as inhibitor of the classical pathway of complement activation. At least two different B. pertussis surface components, one of which is the virulence factor filamentous hemagglutinin (FHA), contribute to the binding. We used a set of C4BP mutants and monoclonal antibodies to characterize the region in C4BP that binds B. pertussis and analyzed the salt sensitivity of the interaction. These studies indicated that positively charged residues at the interface between complement control protein modules 1-2 in the C4BP alpha-chain are important for binding, and that the site in C4BP that binds B. pertussis is very similar, but not identical, to the C4b-binding site. Bacteria-bound C4BP retained its complement regulatory function and B. pertussis selectively bound C4BP in human plasma, indicating that binding occurs also in vivo. Together, these findings indicate that B. pertussis exploits a site in C4BP, resembling that used by the natural ligand C4b.
Berggård
K
K
Department of Medical Microbiology, Dermatology and Infection, Lund University, Lund, Sweden.
Lindahl
G
G
Dahlbäck
B
B
Blom
A M
AM
D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001665:Binding Sites; D001769:Blood / Q000378:metabolism; D001886:Bordetella pertussis / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D015935:Complement C4b / Q000276:immunology / Q000378:metabolism*; D003169:Complement Inactivator Proteins; D003429:Cross Reactions; D004252:DNA Mutational Analysis; D006023:Glycoproteins; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D008024:Ligands; D011951:Receptors, Complement; D012965:Sodium Chloride; D015935:Complement C4b