Copper(II) inhibits in vitro conformational conversion of ovine prion protein triggered by low pH.
To gain insight into the conformational conversion of ovine prion protein (OvPrP(C)) at different pH values and/or in the presence of CuCl(2), the secondary structure of OvPrP(C) was analysed by circular dichroism (CD) spectroscopy. Copper treatment of OvPrP(C) under moderately acidic conditions (pH approximately 5.0-6.0) as well as physiological conditions (pH 7.4) also makes OvPrP(C) adopt protease-resistant and beta-sheet-rich conformation. However, under lower pH conditions (2.0-4.5) with copper treatment, OvPrP(C) gained higher alpha-helix structure. This study demonstrated that Cu(2+) can significantly modulate conformational conversion triggered by acidic pH, and this will provide therapeutic intervention approaches for prion diseases.
National Animal TSE Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Mei-li
ML
Liu
Yu-xing
YX
Li
Xiang-mei
XM
Zhou
De-ming
DM
Zhao
D000818:Animals; D015153:Blotting, Western; D002942:Circular Dichroism; D003300:Copper / Q000494:pharmacology*; D019286:Endopeptidase K / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D034561:Sheep, Domestic / Q000378:metabolism*; D013997:Time Factors
D011328:Prions; D003300:Copper; D019286:Endopeptidase K; C029892:cupric chloride