Different Effect Of Lipid On Conformational Conversion Of Chicken And Murine Prion-protein

Prion disease is caused by the misfolding form of pathogenic prion protein from the normal form of misfolding.Also known as Transmissible Spongiform Encephalopathy（TSE）,prion disease is a class of neurodegenerative diseases that are widely found in mammals.It is thought that the pathogenesis of prion disease is due to the conformation change of prion protein from normal Pr P^Cto abnormal conformation Pr P^Sc.Studies have shown that some of the cofactors involved in the transformation of prion protein from Pr P^Cto Pr P^Scmaybe can promote the conformational transformation of prion protein.Negatively charged polyanions,especially glycosaminoglycans（GAG）polymers,lipids,heparin and nucleic acids（RNA and DNA）have been shown to be an effective cofactor that interacts with prion and undergoes structural changes.As prion proteins are expressed in both mammalian and non-mammalian,only mammals can be sick of this phenomenon.This paper compared the interactions between lipid/heparin and mouse/chicken prion protein to explore the pathogenesis of prion disease.The recombinant prion proteins of mouse and chickens were obtained by affinity chromatography and then interacted with POPG of lipid-bearing and heparin.The amyloid fibril formation assay,the PK resistance test,Th T fluorescence assay,electron microscopy and circular dichroism were used to observe the differences of chicken and mouse prion protein.A series of experiments showed that the negatively charged lipid POPG significantly inhibited the formation of rat recombinant prion protein amyloid fibers and showed more resistance to PK,while the amyloid fibers formed by chicken recombinant prion protein had a slow growth period and low The fluorescence intensity.The effect of heparin on recombinant prion protein in chicken and rat is also different.It can easily cause the conversion of recombinant rat prion protein fromα-helix toβ-sheet,but the effect on chicken recombinant prion protein only affects the insoluble precipitate.It did not affect the changes in its secondary structure.All in all,POPG and heparin are more likely to cause changes in the secondary structure of recombinant mouse prion protein,and for chicken prion protein is not obvious.In this dissertation,the differences in the interactions between lipids and chicken and mouse recombinant prion protein provide clues to understanding the pathogenesis of prion diseases.