A research held at University of California, San Francisco to study the conversion of α helices into β sheets feature in the formation of scrape prion protein.
Prions are infectious particles that are known to cause neurodegenerative disease in humans and animals. Scrapie Prion Proteins (PrPsc) were previously thought to be derived from PrPc via post-translational modification but since attempts to indentify such chemical modifications were unsuccessful this study was designed to examine the possibility that the formation of PrPsc involves conversion of α helices in PrPc to β sheets.
For the sake of this study a PrPc purification protocol was utilized. All chemicals utilized were of the highest grade. Purification of PrPc was modified accordingly to avoid denaturation of PrPc . PrPc, PrPsc and PrP27-30 were purified from Scrapie infected Syrian hamster brains. Purified samples were observed under electron microscope and FTIR spectroscopy was performed on each sample.
FTIR spectroscopy of PrPc showed characteristics features suggestive of high α helix content, on the other hand FTIR spectroscopy of PrPsc showed characteristics of high β sheets content. Meanwhile the secondary structures of PrPc, PrPsc and PrP27-30 were predicted using neural network algorithm. The results obtained were consistent with the hypothesis that it is the conformational change from α helix to β sheets that is responsible for the formation of PrPsc from PrPc.
The study successfully concluded that the formation of PrPsc involves the conversion of α-helices in PrPc into β sheets but the possibility of any other chemical modification cannot be eliminated. The study helped us to recognize that the conversion of α helices on PrPc into β sheets is likely to be the primary lesion in neurodegenerative diseases. Although protein folding is commonly thought to be controlled by thermodynamic preferences, it has been concluded that kinetic issues can alter the folding landscape. In a study done by V. Baskakov, Giuseppe Legname, Stanley B. Prusiner and Fred E. Cohen it was proved that the folding of native PrPC is under kinetic control. So, If a β-rich amyloid competent structure is an intrinsic preference especially at a high protein concentration, then compartmentalization of partially folded intermediates and proteins that mediate unfolding and clearance of misfolded proteins play critical roles in cellular health. In the future we might be able to halt the disease progression by stopping these conformational changes.
Prions are infectious particles that are known to cause neurodegenerative disease in humans and animals. Scrapie Prion Proteins (PrPsc) were previously thought to be derived from PrPc via post-translational modification but since attempts to indentify such chemical modifications were unsuccessful this study was designed to examine the possibility that the formation of PrPsc involves conversion of α helices in PrPc to β sheets.
For the sake of this study a PrPc purification protocol was utilized. All chemicals utilized were of the highest grade. Purification of PrPc was modified accordingly to avoid denaturation of PrPc . PrPc, PrPsc and PrP27-30 were purified from Scrapie infected Syrian hamster brains. Purified samples were observed under electron microscope and FTIR spectroscopy was performed on each sample.
FTIR spectroscopy of PrPc showed characteristics features suggestive of high α helix content, on the other hand FTIR spectroscopy of PrPsc showed characteristics of high β sheets content. Meanwhile the secondary structures of PrPc, PrPsc and PrP27-30 were predicted using neural network algorithm. The results obtained were consistent with the hypothesis that it is the conformational change from α helix to β sheets that is responsible for the formation of PrPsc from PrPc.
The study successfully concluded that the formation of PrPsc involves the conversion of α-helices in PrPc into β sheets but the possibility of any other chemical modification cannot be eliminated. The study helped us to recognize that the conversion of α helices on PrPc into β sheets is likely to be the primary lesion in neurodegenerative diseases. Although protein folding is commonly thought to be controlled by thermodynamic preferences, it has been concluded that kinetic issues can alter the folding landscape. In a study done by V. Baskakov, Giuseppe Legname, Stanley B. Prusiner and Fred E. Cohen it was proved that the folding of native PrPC is under kinetic control. So, If a β-rich amyloid competent structure is an intrinsic preference especially at a high protein concentration, then compartmentalization of partially folded intermediates and proteins that mediate unfolding and clearance of misfolded proteins play critical roles in cellular health. In the future we might be able to halt the disease progression by stopping these conformational changes.
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