Research

Copper(II)-Induced Secondary Structure Changes and Reduced Folding Stability of the Prion Protein


Reference:

Younan, N. D., Klewpatinond, M., Davies, P., Ruban, A. V., Brown, D. R. and Viles, J. H., 2011. Copper(II)-Induced Secondary Structure Changes and Reduced Folding Stability of the Prion Protein. Journal of Molecular Biology, 410 (3), pp. 369-382.

Related documents:

This repository does not currently have the full-text of this item.
You may be able to access a copy if URLs are provided below. (Contact Author)

Official URL:

http://dx.doi.org/10.1016/j.jmb.2011.05.013

Abstract

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 beta-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 beta-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.

Details

Item Type Articles
CreatorsYounan, N. D., Klewpatinond, M., Davies, P., Ruban, A. V., Brown, D. R. and Viles, J. H.
DOI10.1016/j.jmb.2011.05.013
Uncontrolled Keywordsurea, unfolding, circular dichroism, prp, cu(2+)
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code25097

Export

Actions (login required)

View Item