Contributions Of Structural Motifs Of C-reactive Protein In Its Cellular Biogenesis

C-reactive protein (CRP) is a typical human acute phase reactant that is composed of five identical subunits associated with each other non-covalently. It has been proposed that CRP plays an important role in the innate immunity and host defense through regulated conformational changes. However, less is known about the mechanism of cellular folding and assembly of CRP. Several motifs have been identified to be essential for both the structure and function of CRP, including an intra-subunit disulfide bond and binding sites for calcium, PC and Clq. We have analyzed the contributions of these motifs in cellular folding and assembling of CRP by site-directed mutagenesis. Our results reveal that the calcium binding sites and the charged residues on subunit assembly interfaces are critical for the biogenesis of CRP. Interestingly, introduction of inter-subunit disulfide bond resulted in the expression of an unique conformational state of CRP. Our findings provide further insights into the mechanism of CRP folding and assembling.