Molecular Characterization of the Interaction between Porins of Neisseria gonorrhoeae and C4b-Binding Protein.
Författare
Summary, in English
Neisseria gonorrhoeae, the causative agent of gonorrhea, is a natural infection only in humans. The resistance of N. gonorrhoeae to normal human serum killing correlates with porin (Por)-mediated binding to the complement inhibitors C4b-binding protein (CUP). The entire binding site for both porin molecules resides within complement control protein domain 1 (CCPI) of C4BP. Only human and chimpanzee C4BPs bind to Por1B-bearing gonococci, whereas only human C4BP binds to PorlA strains. We have now used these species-specific differences in C4BP binding to gonococci to map the porin binding sites on CCP1 of C4BP. A comparison between human and chimpanzee or rhesus C4BP CCP1 revealed differences at 4 and 12 amino acid positions, respectively. These amino acids were targeted in the construction of 13 recombinant human mutant C4BPs. Overall, amino acids T43, T45, and K24 individually and A12, M14, R22, and L34 together were important for binding to PorlA strains. Altering D15 (found in man) to N15 (found in rhesus) introduced a glycosylation site that blocked binding to PorlA gonococci. C4BP binding to Por1-B strains required K24 and was partially shielded by additional glycosylation in the D15N mutant. Only those recombinant mutant C4BPs that bound to bacteria rescued them from 100% killing by rhesus serum, thereby providing a functional correlate for the binding studies and highlighting C4BP function in gonococcal serum resistance.
Publiceringsår
2007
Språk
Engelska
Sidor
540-547
Publikation/Tidskrift/Serie
Journal of Immunology
Volym
179
Issue
1
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Association of Immunologists
Ämne
- Immunology in the medical area
Status
Published
Forskningsgrupp
- Clinical Chemistry, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1550-6606