期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 36, 期 -, 页码 1288-1292出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST0361288
关键词
copper; misfolding; prion protein; visible circular dichroism
资金
- BBSRC (Biotechnology and Biological Sciences Research Council)
- Biotechnology and Biological Sciences Research Council [BB/D005027/1] Funding Source: researchfish
- BBSRC [BB/D005027/1] Funding Source: UKRI
PrP (prion-related protein) is a cell-surface Cu(2+)-binding glycoprotein which, when misfolded, is responsible for a number of transmissible spongiform encephalopathies. The co-ordination geometry, stoichiometry and affinity of Cu(2+) 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 Cu(2+) ions bind to PrP with submicromolar affinity. initially, two Cu(2+) ions bind to full-length PrP in the amyloidogenic region, between the octarepeats and the structured domain, at His(95) and His(110). only subsequent Cu(2+) 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 Cu(2+) bound to full-length PrP; this approach places the affinity in the nanomolar range. The affinity and number of Cu(2+)-binding sites support the suggestion that PrP could act as an antioxidant by binding potentially harmful Cu(2+) ions and sacrificially quenching of free radicals generated as a result of copper redox cycling. Finally, the effect of Cu(2+) on the prion structure and misassembly into oligomers and fibres is discussed.
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