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C-reactive protein binds to phosphorylated carbohydrates
F J Culley1, K B Bodman-Smith, M A Ferguson
1Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK and.
Glycobiology
|November 26, 1999
Summary
C-reactive protein (CRP) binds strongly to phosphorylated carbohydrates on Leishmania parasites. Optimal binding requires specific structures, suggesting CRP may target microbial surfaces.
Area of Science:
- Immunology
- Biochemistry
- Parasitology
Background:
- C-reactive protein (CRP) is a key acute phase protein in humans.
- Understanding CRP's physiological role requires investigating its binding interactions.
- Leishmania donovani parasites possess lipophosphoglycan, a major surface glycoconjugate.
Purpose of the Study:
- To identify and characterize the binding interactions of C-reactive protein (CRP) with specific carbohydrate structures.
- To define the structural features of carbohydrate ligands that mediate high-avidity binding to CRP.
- To explore the potential role of CRP in recognizing microbial surfaces.
Main Methods:
- Chemically synthesized carbohydrate ligands representing Leishmania lipophosphoglycan.
- Competition assays using various monosaccharides (amino, sulfated, phosphorylated, unsubstituted) to inhibit CRP binding.
- Synthesis and testing of oligosaccharides and phospho-oligosaccharides of varying lengths and conformations.
Main Results:
- Demonstrated high-avidity binding of CRP to a synthetic carbohydrate ligand mimicking Leishmania lipophosphoglycan.
- Phosphorylated monosaccharides were the only effective inhibitors of CRP binding, indicating the importance of phosphorylation.
- Optimal CRP recognition involved a single phosphate group situated between two monosaccharide pyranose rings in a linear molecule.
Conclusions:
- CRP binding avidity is influenced by both the carbohydrate structure and the position of phosphorylation.
- The interaction between CRP's binding site, the carbohydrate, and the phosphate group is crucial for recognition.
- CRP may function by recognizing extensive arrays of phosphorylated carbohydrates found on microbial surfaces.