期刊
BIOCHEMICAL JOURNAL
卷 404, 期 -, 页码 393-402出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20061893
关键词
CD; copper binding; EPR; metal co-ordination; prion protein (PrP); spectroscopy
资金
- Biotechnology and Biological Sciences Research Council [BB/D005027/1] Funding Source: Medline
- Medical Research Council [MC_U117533887] Funding Source: Medline
- BBSRC [BB/D005027/1] Funding Source: UKRI
- MRC [MC_U117533887] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D005027/1] Funding Source: researchfish
- Medical Research Council [MC_U117533887] Funding Source: researchfish
The prion protein (PrP) is a Cu2+-binding cell-surface glycoprotein. Using various PrP fragments and spectroscopic techniques, we show that two Cu2+ ions bind to a region between residues 90 and 126. This region incorporates the neurotoxic portion of PrP, vital for prion propagation in transmissible spongiform encephalopathies. Pentapeptides PrP-(92-96) and PrP-(107-111) represent the minimum motif for Cu2+ binding to the PrP-(90-126) fragment. Consequently, we were surprised that the appearance of the visible CD spectra for two fragments of PrP, residues 90126 and 91-115, are very different. We have shown that these differences do not arise from a change in the co-ordination geometry within the two fragments; rather, there is a change in the relative preference for the two binding sites centred at His(111) and His(96). These preferences are metal-, pH- and chain-length dependent. CD indicates that Cu2+ initially fills the site at His(111) within the PrP-(90-126) fragment. The pH-dependence of the Cu2+ co-ordination is studied using EPR, visible CD and absorption spectroscopy. We present evidence that, at low pH (5.5) and substoichiometric amounts of Cu2+, a multiple histidine complex forms, but, at neutral pH, Cu2+ binds to individual histidine residues. We have shown that changes in pH and levels of extracellular Cu2+ will affect the co-ordination mode, which has implications for the affinity, folding and redox properties of Cu-PrP.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据