title: C-reactive protein binds to phosphorylated carbohydrates.
abstract: C-reactive protein (CRP) is a major acute phase protein in man. In order to more fully understand the physiological role of this serum protein, we have demonstrated high avidity binding for a defined chemically synthesized carbo-hydrate ligand which represents the repeating disaccharide of lipophosphoglycan, the major surface glycoconjugate of the unicellular parasite Leishmania donovani. Increasing the number of phosphorylated disaccharides in a molecule from one up to seven did not increase the avidity for CRP, however increasing this to 10 potential CRP binding sites did. In order to define the important features of this complex and variable structure for CRP binding we competed CRP binding to whole Leishmania parasites with amino, sulfated, phosphorylated, and unsubstituted monosaccharides, of which only phosphorylated monosaccharides were able to inhibit. Both the carbohydrate and the position of phosphorylation influenced the avidity for CRP. Synthetic oligosaccharides and phospho-oligosaccharides of various lengths and conformations were used to define the structural requirements for CRP recognition. The optimum structure for recognition of a single phosphate group was between two monosaccharide pyranose rings, and within a linear rather than a cyclic molecule. This stresses the importance of the interaction of the CRP binding site with both the carbohydrate and the phosphate group. CRP function may be mediated via the recognition of large arrays of phosphorylated carbohydrates as are characteristic of the surface of microorganisms.
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK and.
authors.forename: F J
authors.initials: FJ
authors.lastname: Culley
authors.forename: K B
authors.initials: KB
authors.lastname: Bodman-Smith
authors.forename: M A
authors.initials: MA
authors.lastname: Ferguson
authors.forename: A V
authors.initials: AV
authors.lastname: Nikolaev
authors.forename: N
authors.initials: N
authors.lastname: Shantilal
authors.forename: J G
authors.initials: JG
authors.lastname: Raynes
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: D004187:Disaccharides; D037102:Lectins; D002097:C-Reactive Protein