Prion Protein Conversion and Lipids
The conversion of α-helical rich normal prion protein to a β-sheeted pathogenic isoform is central to the pathogenesis of prion disease. Recent studies have revealed the importance of cofactors in prion protein conformal change and in generating prion infectivity. Lipid appears to be a critical cofactor because of its unique biophysical properties and its ability to induce protein conformational changes. Biophysical and biochemical analyses of lipid–prion protein interactions and the resulting prion protein conformational changes revealed a huge impact of lipids on prion protein conformation. Studies of disease-associated mutations and the generation of highly infectious prions with bacterially expressed recombinant prion protein in the presence of lipid support the relevance of lipid interaction to prion disease. The hypothesized roles of lipid in prion protein conversion require rigorous future researches, which are essential for unveiling the molecular mechanism of prion infectivity.
KeywordsPrion protein Prion protein conversion Lipids TSEs Prion infectivity
Thanks to Xinhe Wang, Fei Wang, and Jessica Chadwick at Ohio State University for comments and thanks to Fei Wang for generating the images with PyMOL.
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