Research On Mechanism Of Interaction Between Monomeric C-reactive Protein And Ligands

The classical acute-phase protein,C-reactive protein(CRP),is not only a strong marker for predicting future cardiovascular events,but also a direct partaker that mediates pathogenesis of atherosclerotic cardiovascular disease.CRP has two types of isoforms:native pentameric CRP(pCRP)and monomeric CRP(mCRP).Recently research identified a dissociation mechanism leading to a conformational change from the pCRP to mCRP,suggesting that CRP participates in localized pathological process via mCRP.CRP acts with various intrinsic and extrinsic ligands playing a vital role in the innate immune system.Thus,research on mCRP-ligands interaction provides a new method to cure diseases,such as inflammation and atherosclerosis.In the present study,we first selected some important ligands which were tested respectively of the half saturated concentration of binding between mCRP and ligands.Then,in the condition of this half saturated binding,we used mCRP-derived peptides to interrupt it.The results showed that only one peptide whose amino acid sequence corresponds to the 35-47 position of mCRP(peptide 35-47)can obviously inhibit the binding of mCRP to all ligands at low concentrations,and the biggest difference among peptide 35-47 and other peptides is only the amino acid sequences.According to the above,we believe that the interaction between mCRP and ligands is most likely mediated by the 35-47 amino acid sequence of mCRP.Then,we transformed and modified peptide 35-47 to keep on interrupt the interaction between mCRP and ligands.We further found that N-terminal of peptide 35-47 is more important during the interaction and after replacing L-amino-acids to D-amino-acids,its efficiency of competition has been obviously improved.