The Study Of Process Of Folding And Unfolding Of C-reactive Protein

C-reactive protein(CRP)is an acute phase plasma protein and its plasma concentration could increase 2-3 orders of magnitude to 1000-fold or more after the hours of the generation of acute inflammatory stimulation signals.CRP is highly conserved and homologous in vertebrates and many invertebrate.It's a part of the innate response,injuries and/or diseases that affect systemic/local inflammation could trigger cellular damage,and then the CRP could mainly release from the liver to blood to neutralizing pathogen.As a result,it could be an appropriate biomarker of inflammation.CRP also has many biological functions as activating the classical complement pathway through directly binding to C1 q and enhancing leukocyte phagocytosis of bacteria through binding to Fc immunoglobulin receptors(Fc?R).Protein after translation must have the proper 3D spatial conformation to performing its correct biological functions.The process of folding is very accurate but complex.There is a great challenge for scientific community to finding and solving the general law of protein folding.CRP belongs to the family of short chain pentraxins and consists of 5 identical monomers with noncovalent bond.It can't be renatured spontaneously in vitro but the SAP and zebra fish CRP that share similar sequential and conformational features can be renatured in proper solution in vitro.This phenomenon may suggest that CRP has a specific mechanism of folding.Up to now,many conformations of CRP have been discovered,such as the pentameric CRP(pCRP)and monomeric CRP(mCRP).Because of these two isoforms of CRP have both similar and different physiological functions,for instance,both they can bind to C1 q and factor H to regulating the classical complement pathway,but mCRP has higher affinity to binding factor H and could bind to C4 bp to regulate the classical complement pathway as well.As a result,this phenomenon may exist special mechanism through the conformation changing.The purpose of study is investigating the process of folding and unfolding in order to helping us finding the underlying mechanism of conformational changes of CRP.Using single-molecule atomic force microscopy(AFM)though firstly constructing polypeptides that contain different conformational regions of CRP and molecule dynamic simulation(MDS)as a supplementary method to researching the whole process of folding and unfolding.For the results,our goal is finding the intermediated and functional sites to explain the mechanism of conformational change of CRP.