Send to

Choose Destination
J Mol Biol. 2011 Jul 15;410(3):369-82. doi: 10.1016/j.jmb.2011.05.013. Epub 2011 May 17.

Copper(II)-induced secondary structure changes and reduced folding stability of the prion protein.

Author information

School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK.


The cellular isoform of the prion protein PrP(C) is a Cu(2)(+)-binding cell surface glycoprotein that, when misfolded, is responsible for a range of transmissible spongiform encephalopathies. As changes in PrP(C) conformation are intimately linked with disease pathogenesis, the effect of Cu(2+) ions on the structure and stability of the protein has been investigated. Urea unfolding studies indicate that Cu(2+) ions destabilise the native fold of PrP(C). The midpoint of the unfolding transition is reduced by 0.73 ± 0.07 M urea in the presence of 1 mol equiv of Cu(2+). This equates to an appreciable difference in free energy of unfolding (2.02 ± 0.05 kJ mol(-1) at the midpoint of unfolding). We relate Cu(2)(+)-induced changes in secondary structure for full-length PrP(23-231) to smaller Cu(2)(+) binding fragments. In particular, Cu(2+)-induced structural changes can directly be attributed to Cu(2+) binding to the octarepeat region of PrP(C). Furthermore, a β-sheet-like transition that is observed when Cu ions are bound to the amyloidogenic fragment of PrP (residues 90-126) is due only to local Cu(2+) coordination to the individual binding sites centred at His95 and His110. Cu(2+) binding does not directly generate a β-sheet conformation within PrP(C); however, Cu(2+) ions do destabilise the native fold of PrP(C) and may make the transition to a misfolded state more favourable.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center