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Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid
- Source :
- Journal of Immunology, Journal of Immunology, 2014, 193 (11), pp.5699-5708. ⟨10.4049/jimmunol.1400127⟩, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2014, 193 (11), pp.5699-5708. ⟨10.4049/jimmunol.1400127⟩
- Publication Year :
- 2014
-
Abstract
- Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal clinical isolates, but its ligands and especially its molecular specificity remain to be identified. Using solid-phase binding assays, serum and recombinant L-ficolins were shown to interact with serotype 2 pneumococcal strain D39 and its unencapsulated R6 derivative. Incubation of both strains with serum triggered complement activation, as measured by C4b and C3b deposition, which was decreased by using ficolin-depleted serum. Recombinant L-ficolin and its FBG-like recognition domain bound to isolated pneumococcal cell wall extracts, whereas binding to cell walls depleted of teichoic acid (TA) was decreased. Both proteins were also shown to interact with two synthetic TA compounds, each comprising part structures of the complete lipoteichoic acid molecule with two PCho residues. Competition studies and direct interaction measurements by surface plasmon resonance identified PCho as a novel L-ficolin ligand. Structural analysis of complexes of the FBG domain of L-ficolin and PCho revealed that the phosphate moiety interacts with amino acids previously shown to define an acetyl binding site. Consequently, binding of L-ficolin to immobilized acetylated BSA was inhibited by PCho and synthetic TA. Binding of serum L-ficolin to immobilized synthetic TA and PCho-conjugated BSA triggered activation of the lectin complement pathway, thus further supporting the hypothesis of L-ficolin involvement in host antipneumococcal defense.
- Subjects :
- Proteases
[SDV]Life Sciences [q-bio]
Phosphorylcholine
Immunology
Plasma protein binding
Biology
Pneumococcal Infections
chemistry.chemical_compound
Cell Wall
Lectins
Complement C4b
Immunology and Allergy
Humans
Binding site
Complement Activation
Phosphocholine
chemistry.chemical_classification
Teichoic acid
Fibrinogen
Acetylation
Surface Plasmon Resonance
Immunity, Innate
Complement system
Amino acid
Protein Structure, Tertiary
Teichoic Acids
Streptococcus pneumoniae
chemistry
Biochemistry
Complement C3b
Host-Pathogen Interactions
[SDV.IMM]Life Sciences [q-bio]/Immunology
Lipoteichoic acid
Protein Binding
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 193
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....931e3f89fd3b3cf74adf7e9b0b2c1da8