Multiple Forms of Copper (Ii) Co-ordination Occur Throughout the Disordered N-terminal Region of the Prion Protein at Ph 7.4.
From: Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.
The Biochemical journal
- Publish Date: Dec 2006
- ISSN: 1470-8728
- Volume: 400
- Issue: 3
- Pages: 501-10
- Medium: Internet
- Language: English
- Citation (JAMA): Wells Mark A, Jelinska Clare, Hosszu Laszlo L P, et al. Multiple Forms of Copper (Ii) Co-ordination Occur Throughout the Disordered N-terminal Region of the Prion Protein at Ph 7.4.. Biochem. J. Dec 2006;400:501-10
Abstract
Although the physiological function of the prion protein remains unknown, in vitro experiments suggest that the protein may bind copper (II) ions and play a role in copper transport or homoeostasis in vivo. The unstructured N-terminal region of the prion protein has been shown to bind up to six copper (II) ions, with each of these ions co-ordinated by a single histidine imidazole and nearby backbone amide nitrogen atoms. Individually, these sites have micromolar affinities, which is weaker than would be expected of a true cuproprotein. In the present study, we show that with subsaturating levels of copper, different forms of co-ordination will occur, which have higher affinity. We have investigated the copper-binding properties of two peptides representing the known copper-binding regions of the prion protein: residues 57-91, which contains four tandem repeats of the octapeptide GGGWGQPH, and residues 91-115. Using equilibrium dialysis and spectroscopic methods, we unambiguously demonstrate that the mode of copper co-ordination in both of these peptides depends on the number of copper ions bound and that, at low copper occupancy, copper ions are co-ordinated with sub-micromolar affinity by multiple histidine imidazole groups. At pH 7.4, three different modes of copper co-ordination are accessible within the octapeptide repeats and two within the peptide comprising residues 91-115. The highest affinity copper (II)-binding modes cause self-association of both peptides, suggesting a role for copper (II) in controlling prion protein self-association in vivo.
Mesh Headings (Keywords): Binding Sites, Copper, Humans, Hydrogen-Ion Concentration, Molecular Structure, Prions, Protein Binding
Check for Full Text / PubMed Unique Identifier (PMID): 16925523
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