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Copper coordination in the full-length, recombinant prion protein
Colin S Burns1, Eliah Aronoff-Spencer, Giuseppe Legname
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Biochemistry
|June 5, 2003
Summary
The prion protein (PrP) binds copper in its octarepeat domain and a newly identified site involving His96. PrP
Area of Science:
- Biochemistry
- Biophysics
- Neuroscience
Background:
- The prion protein (PrP) binds copper, suggesting roles in copper regulation or enzyme activity.
- Copper binding sites in PrP are primarily located in the octarepeat domain (PHGGGWGQ).
- Previous studies identified the HGGGW segment as a key copper-binding unit within octarepeats.
Purpose of the Study:
- To characterize the molecular features of copper binding sites in full-length Syrian hamster PrP.
- To investigate the involvement of His96 in copper binding.
- To determine the pH-dependence of copper binding to PrP.
Main Methods:
- Electron Paramagnetic Resonance (EPR) spectroscopy (X-band and S-band).
- Electron spin-echo envelope spectroscopy (ESE).
- Utilized recombinant full-length Syrian hamster PrP and various PrP peptide constructs.
Main Results:
- Four copper ions bind within the octarepeat domain, confirming prior findings.
- A fifth copper binding site was identified in the flexible region, involving His96 (PrP(92-96) segment GGGTH).
- This fifth site's copper affinity is pH-dependent, with binding lost below pH 6.0.
Conclusions:
- A comprehensive profile of copper binding sites in PrP has been established.
- The findings support the hypothesis that PrP's function is linked to its pH-dependent copper-binding capabilities.