Different effects of lipid on conformational conversion of chicken and murine prion proteins.

Prion diseases are characterized by the conformational conversion of the cellular prion protein (PrP) to the pathogenic isoform (PrP). Lipids have been found to interact with PrP and contribute to the efficient formation of PrP. Non-mammalian PrPs are not readily to undergo the conversion process into an infectious isoform, yet the effect of lipid on the conformational conversion of non-mammalian PrP remains to be explored. Herein, the effects of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) on full-length recombinant chicken PrP (ChPrP) 24-249 and murine PrP (MoPrP) 23-230 were investigated. Firstly, it was found that in the presence of chemical denaturant, POPG remarkably inhibited MoPrP amyloid fibril growth, while had slight effect on that of ChPrP as estimated by amyloid fibril growth and transmissible electronic microscope assays. Secondly, under physiological condition, POPG induced conformation changes in both MoPrP and ChPrP using Thioflavin T (ThT) fluorescence, circular dichroism, proteinase K digestion and transmission electron microscopy assays. With a POPG:PrP molar ratio of 30:1, the ThT fluorescence of MoPrP was found to be lower than that of ChPrP, however, the POPG-induced MoPrP had higher β-sheet content and was more proteinase K-resistant than POPG-induced ChPrP. In summary, the present results suggested that the effects of POPG on conformational conversion of MoPrP and ChPrP were different under both denaturation and physiological conditions.