The Research Of CRP's Folding And Unfolding Process

C-reactive protein(CRP)is an unspecific marker of inflammation and it has been used as a detective method in clinical.CRP is widely distributed in both vertebrate and invertebrate with conservation in evolution.There is no deficiency and no polymorphism in human being implicating that CRP plays a critical role in vivo.But,there are still many controversies in this area.We can't describe the precise function of CRP in vivo.In recent years,researchers found that CRP was not only a marker of inflammation but also a predictor of cardiovascular disease.The base level concentration of CRP is connected to the atherogenesis.More and more evidence suggest that CRP is not only a marker or a predictor but also a participator in inflammatory regulation and atherogenesis.Investigating the exact molecular mechanism of CRP may provide a way in healing the related diseases.There are two natural isoforms of CRP in human.One is the pentameric CRP(pCRP)which include five identical subunits,the other one is the monomeric CRP(mCRP)which only have one subunit.The two isoforms exhibit some similarities,such as the ability to bind to Clq to activate the classic complement.But there are obvious differences between them.Although both of the two isoforms can activate endothelial cells,the stimulating intensity of mCRP is much stronger than the pCRP.Factor H and oxLDL are more likely to bind to the mCRP rather than the pCRP.And C4bp only bind to the mCRP,not to the pCRP.So the transition of the conformation from the pentamer to the monomer may present the active regulatory mechanism of CRP.The pCRP may present the rest state of CRP and the mCRP maybe the activated state of CRP.The conformational change can expose new functional site to exert some new functions.If the hypothesis can be supported,the controversy may be explained.Our research is to investigate the folding and unfolding process of CRP which can help us to understand the mechanism of the conformational change.The structure of pCRP is very stable in physiological condition.It's hard to completely dissociate the pentameric structure without using the denatured methods.We hope to measure the interaction force inside the molecular during the folding and unfolding process with atomic force microscopy(AFM).And using molecular dynamic simulation and spectrum experiment as supplementary to describe the process of folding and unfolding.The result may help to explain how the conformational change of CRP under physiological condition in vivo.