The amyloidogenic region of the human prion protein contains a high affinity (Met)(2)(His)(2) Cu(I) binding site

Badrick, AC and Jones, CE (2009) The amyloidogenic region of the human prion protein contains a high affinity (Met)(2)(His)(2) Cu(I) binding site. Journal of Inorganic Biochemistry, 103 8: 1169-1175. doi:10.1016/j.jinorgbio.2009.06.005


Author Badrick, AC
Jones, CE
Title The amyloidogenic region of the human prion protein contains a high affinity (Met)(2)(His)(2) Cu(I) binding site
Formatted title
The amyloidogenic region of the human prion protein contains a high affinity (Met)2(His)2 Cu(I) binding site
Journal name Journal of Inorganic Biochemistry   Check publisher's open access policy
ISSN 0162-0134
Publication date 2009-06-25
Sub-type Article (original research)
DOI 10.1016/j.jinorgbio.2009.06.005
Open Access Status
Volume 103
Issue 8
Start page 1169
End page 1175
Total pages 7
Editor Dr. J H Dawson
Place of publication United States
Publisher Elsevier Inc.
Language eng
Subject C1
030201 Bioinorganic Chemistry
030207 Transition Metal Chemistry
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
920112 Neurodegenerative Disorders Related to Ageing
Abstract The prion protein (PrP) is a cuproprotein implicated in a number of human neurodegenerative diseases. Although many physiological functions have been ascribed to PrP, its potential to act as a neuronal antioxidant, based in part on its copper binding ability, is controversial and unresolved. A number of studies have shown that copper bound to PrP is not redox silent, and recent data shows that the Cu(II) sites at histidines 96 and 111 display reversible electrochemistry. Reversible electrochemistry implies redox cycling whilst the metal remains bound and with the absence of permanent oxidation or reduction of the protein. Despite this indirect evidence of Cu(I) binding to PrP, the nature of the Cu(I) binding site/s is unclear, although previous extended X-ray absorption fine structure (EXAFS) data has implicated methionines in the Cu(I) binding site. Using spectroscopic techniques we find that the PrP region encompassing histidines 96 and 111 can bind a Cu(I) ion in a site comprising His 96, His 111, Met 109 and Met 112. The four-coordinate (His)(Met) Cu(I) site has a K = 10-10 M indicative of high affinity. Mutation of histidine residues reduces the Cu(I) affinity. Although alluding to the fact the PrP could act in a direct superoxide dismutase-like fashion, the Cu(I)-PrP(91-124) site and affinity is comparable to that observed for bacterial periplasmic Cu(I) transporters.
Keyword Copper
Prion
Neurodegeneration
Peptide
NMR
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 03 Sep 2009, 17:44:02 EST by Mr Andrew Martlew on behalf of School of Chemistry & Molecular Biosciences