PrP (prion-related protein) is a cell-surface Cu2+-binding glycoprotein which, when misfolded, is responsible for a number of transmissible spongiform encephalopathies. The co-ordination geometry, stoichiometry and affinity of Cu2+ for PrP are the subject of much debate. In the present paper, we review the recent progress we have made in these areas. As many as six Cu2+ ions bind to PrP with submicromolar affinity. Initially, two Cu2+ ions bind to full-length PrP in the amyloidogenic region, between the octarepeats and the structured domain, at His95 and His110. Only subsequent Cu2+ ions bind to single histidine residues within the octarepeat region. Competitive chelators have been used to determine the affinity of the first molar equivalent of Cu2+ bound to full-length PrP; this approach places the affinity in the nanomolar range. The affinity and number of Cu2+-binding sites support the suggestion that PrP could act as an antioxidant by binding potentially harmful Cu2+ ions and sacrificially quenching of free radicals generated as a result of copper redox cycling. Finally, the effect of Cu2+ on the prion structure and misassembly into oligomers and fibres is discussed.
Skip Nav Destination
Article navigation
December 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
November 19 2008
Copper and the structural biology of the prion protein
John H. Viles;
John H. Viles
1
1School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, U.K.
1To whom correspondence should be addressed (email j.viles@qmul.ac.uk).
Search for other works by this author on:
Mark Klewpatinond;
Mark Klewpatinond
1School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, U.K.
Search for other works by this author on:
Rebecca C. Nadal
Rebecca C. Nadal
1School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 29 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (6): 1288–1292.
Article history
Received:
August 29 2008
Citation
John H. Viles, Mark Klewpatinond, Rebecca C. Nadal; Copper and the structural biology of the prion protein. Biochem Soc Trans 1 December 2008; 36 (6): 1288–1292. doi: https://doi.org/10.1042/BST0361288
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.