Abstract
The conversion of cellular prion protein (PrPC) to disease-provoking conformer (PrPSc) is crucial in the pathogenesis of prion diseases. Heparin has been shown to enhance mammalian prion protein misfolding. As spontaneous prion disease has not been reported in non-mammalian species, such as chicken, it is interesting to explore the influence of heparin on the conversion of chicken prion protein (ChPrP). Herein, we investigated the influences of heparin on biochemical properties of full-length recombinant ChPrP, with murine prion protein (MoPrP) as control. The results showed that at low heparin concentration (10 μg/mL), a great loss of solubility was observed for both MoPrP and ChPrP using solubility assays. In contrast, when the concentration of heparin was high (30 μg/mL), the solubility of MoPrP and ChPrP both decreased slightly. Using circular dichroism, PK digestion and transmission electron microscopy, significantly increased β-sheet content, PK resistance and size of aggregates were observed for MoPrP interacted with 30 μg/mL heparin, whereas 30 μg/mL heparin-treated ChPrP showed less PK resistance and slight increase of β-sheet structure. Therefore, heparin can induce conformational changes in both MoPrP and ChPrP and the biochemical properties of the aggregates induced by heparin could be modified by heparin concentration. These results highlight the importance of concentration of cofactors affecting PrP misfolding.