A Novel Sialic Acid Binding Site on Factor H Mediates Serum Resistance of Sialylated Neisseria gonorrhoeae

@article{Ram1998ANS,
  title={A Novel Sialic Acid Binding Site on Factor H Mediates Serum Resistance of Sialylated Neisseria gonorrhoeae},
  author={Sanjay Ram and Ajay Sharma and Scott D. Simpson and Sunita Gulati and Daniel P McQuillen and Michael K. Pangburn and Peter A. Rice},
  journal={The Journal of Experimental Medicine},
  year={1998},
  volume={187},
  pages={743 - 752}
}
Factor H (fH), a key alternative complement pathway regulator, is a cofactor for factor I–mediated cleavage of C3b. fH consists of 20 short consensus repeat (SCR) domains. Sialic acid binding domains have previously been localized to fH SCRs 6–10 and 13. To examine fH binding on a sialylated microbial surface, we grew Neisseria gonorrhoeae in the presence of 5′-cytidinemonophospho-N-acetylneuraminic acid, which sialylates lipooligosaccharide and converts to serum resistance gonococci previously… Expand
Biophysical analysis of sialic acid recognition by the complement regulator Factor H
TLDR
This work characterized FH’s sialylation with respect to glycosidic linkage type and searched for further potential sialic acid binding sites in FH and its seven-domain spanning splice variant and fellow complement regulator FH like-1 (FHL-1), and probed FH binding to the sIALic acid variant Neu5Gc. Expand
Binding of Complement Factor H to Loop 5 of Porin Protein 1A: A Molecular Mechanism of Serum Resistance of Nonsialylated Neisseria gonorrhoeae
TLDR
It is demonstrated that Por1A bearing gonococcal strains bind more factor H, a critical downregulator of the alternative complement pathway, than their Por1B counterparts, which results in a sevenfold reduction in C3b, which is >75% converted to iC3b. Expand
Binding of Complement Factor H to Loop 5 of Porin Protein 1A: A Molecular Mechanism of Serum Resistance of Nonsialylated Neisseria gonorrhoeae
TLDR
It is demonstrated that Por1A bearing gonococcal strains bind more factor H, a critical downregulator of the alternative complement pathway, than their Por1B counterparts, which results in a sevenfold reduction in C3b, which is >75% converted to iC3b. Expand
Structural basis for sialic acid-mediated self-recognition by complement factor H.
TLDR
The crystal structure of a ternary complex formed by the two C-terminal domains of FH, a sialylated trisaccharide and the complement C3b thioester-containing domain is solved, finding that the FH sialic acid binding site is structurally homologous to the binding sites of two evolutionarily unrelated proteins. Expand
Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein from Neisseria meningitidis and the Binding of Factor H SCR 18 to 20 to Neisseria gonorrhoeae Porin
TLDR
Findings may provide the molecular basis for recent observations that demonstrated human-specific fH binding to meningococci and may be important for modulating their individual responses to host immune attack. Expand
Molecular Characterization of the Interaction between Sialylated Neisseria gonorrhoeae and Factor H*
TLDR
Findings provide further insights into the species specificity of gonococcal infections and proof-of-concept of a novel therapeutic approach against gonorrhea, a disease rapidly becoming resistant to conventional antibiotics. Expand
Human Factor H Interacts Selectively with Neisseria gonorrhoeae and Results in Species-Specific Complement Evasion1
TLDR
Direct-binding specificity of HufH only to gonococci that prevents serum killing is restricted to humans and may in part explain species-specific restriction of natural gonococcal infection. Expand
Role of Gonococcal Neisserial Surface Protein A (NspA) in Serum Resistance and Comparison of Its Factor H Binding Properties with Those of Its Meningococcal Counterpart
TLDR
The role for NspA is highlighted in enabling N. gonorrhoeae to subvert complement despite LOS phase variation and knowledge of FH-NspA interactions will inform the design of vaccines and immunotherapies against the global threat of multidrug-resistant gonorrhea. Expand
Binding of C 4 b-binding protein : A molecular mechanism of serum resistance of Neisseria gonorrhoeae
We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-bindingExpand
Acquisition of factor H by a novel surface protein on group B Streptococcus promotes complement degradation
TLDR
The identification of the SHT as an FH‐binding protein on the surface of GBS type III is revealed, revealing a novel mechanism by which the bacterium acquires FH to evade complement opsonization. Expand
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