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The N-Terminal Tandem Repeat Region of Human Prion Protein Reduces Copper: Role of Tryptophan Residues

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Abstract

Prion protein (PrP) has attracted considerable attention, mainly due to its involvement in transmissible spongiform encephalopathies. Toward its N-terminal region, PrP bears an octapeptide repeat which has been shown to bind copper. We found that a human synthetic peptide (PrP59–91), corresponding to the four repeats of Pro-His-Gly-Gly-Gly-Trp-Gly-Gln has the ability to reduce copper. A mutant peptide lacking tryptophan displayed only 24% of the wild-type copper-reducing activity. Experiments performed in a N2 environment confirmed that O2 is not involved in the reaction. Our results indicated that cell surface PrP, besides its ability to bind copper, bears the capacity to reduce copper in vitro. The potential physiological role of copper reduction by PrP is discussed.

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Abbreviations used: PrP, prion protein; β-APP, β-amyloid precursor protein; β-APP135-156, copper binding domain of β-amyloid precursor protein; BC, bathocuproine disulfonic acid disodium salt; PBS, phosphate-buffered saline; PrPC, normal cellular form of prion protein; PrPSc, pathogenic form of prion protein; PrP59–91, copper binding domain of prion protein; Aβ, amyloid-β-peptide

1

To whom correspondence and reprint requests should be addressed at the Molecular Neurobiology Unit, Pontifical Catholic University of Chile, P.O. Box 114-D, Santiago, Chile. Fax: 56-2-6862717. E-mail: [email protected].

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