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.
Liu
Mei-li
ML
National Animal TSE Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Li
Yu-xing
YX
Zhou
Xiang-mei
XM
Zhao
De-ming
DM
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