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Molecular Characterization of the Interaction between Porins of Neisseria gonorrhoeae and C4b-Binding Protein.

Jarva, Hanna LU ; Ngampasutadol, Jutamas; Ram, Sanjay; Rice, Peter A; Villoutreix, Bruno O and Blom, Anna LU (2007) In Journal of Immunology 179(1). p.540-547
Abstract
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.... (More)
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. (Less)
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author
organization
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Contribution to journal
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published
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in
Journal of Immunology
volume
179
issue
1
pages
540 - 547
publisher
American Association of Immunologists
external identifiers
  • wos:000247497600064
  • scopus:34250823430
ISSN
1550-6606
language
English
LU publication?
yes
id
360fce6a-7815-4d96-b71d-cefc9a29a3b3 (old id 539708)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17579075&dopt=Abstract
date added to LUP
2007-12-12 12:52:49
date last changed
2017-01-01 07:24:30
@article{360fce6a-7815-4d96-b71d-cefc9a29a3b3,
  abstract     = {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.},
  author       = {Jarva, Hanna and Ngampasutadol, Jutamas and Ram, Sanjay and Rice, Peter A and Villoutreix, Bruno O and Blom, Anna},
  issn         = {1550-6606},
  language     = {eng},
  number       = {1},
  pages        = {540--547},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Molecular Characterization of the Interaction between Porins of Neisseria gonorrhoeae and C4b-Binding Protein.},
  volume       = {179},
  year         = {2007},
}