Affinity of C-reactive protein toward FcgammaRI is strongly enhanced by the gamma-chain.

C-reactive protein (CRP), the prototype human acute phase protein, is widely regarded as a key player in cardiovascular disease, but the identity of its cellular receptor is still under debate. By using ultrasensitive confocal imaging analysis, we have studied CRP binding to transfected COS-7 cells expressing the high-affinity IgG receptor FcgammaRI. Here we show that CRP binds to FcgammaRI on intact cells, with a kd of 10+/-3 micromol/L. Transfection of COS-7 cells with a plasmid coding for both FcgammaRI and its functional counterpart, the gamma-chain, markedly increases CRP affinity to FcgammaRI, resulting in a kd of 0.35+/-0.10 micromol/L. The affinity increase results from an approximately 30-fold enhanced association rate coefficient. The pronounced enhancement of affinity by the gamma-chain suggests its crucial involvement in the CRP receptor interaction, possibly by mediating interactions between the transmembrane moieties of the receptors. Dissociation of CRP from the cell surfaces cannot be detected throughout the time course of several hours and is thus extremely slow. Considering the pentameric structure of CRP, this result indicates that multivalent binding and receptor clustering are crucially involved in the interaction of CRP with nucleated cells.

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