C-reactive protein binds to phosphorylated carbohydrates

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 hav e demonstrated high avidity binding for a defined chemically synthesized ca rbohydrate ligand which represents the repeating disaccharide of lipophosph oglycan, the major surface glycoconjugate of the unicellular parasite Leish mania 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 bindi ng we competed CRP binding to whole Leishmania parasites with amino, sulfat ed, phosphorylated, and unsubstituted monosaccharides, of which only phosph orylated monosaccharides were able to inhibit. Both the carbohydrate and th e position of phosphorylation influenced the avidity for CRP, Synthetic oli gosaccharides and phospho-oligosaccharides of various lengths and conformat ions were used to define the structural requirements for CRP recognition. T he optimum structure for recognition of a single phosphate group was betwee n two monosaccharide pyranose rings, and within a linear rather than a cycl ic molecule. This stresses the importance of the interaction of the CRP bin ding site with both the carbohydrate and the phosphate group. CRP function may be mediated via the recognition of large arrays of phosphorylated carbo hydrates as are characteristic of the surface of microorganisms.