Copper(II) binding to the human Doppel protein may mark its functional diversity from the prion protein.

The Journal of Biological Chemistry
Grazia M CereghettiSabine Van Doorslaer

Abstract

Doppel (Dpl) is the first described homologue of the prion protein, the main constituent of the agent responsible for prion diseases. The cellular prion protein (PrP(C)) is predominantly present in the central nervous system. Although its role is not yet completely clarified, PrP(C) seems to be involved in Cu(2+) recycling from synaptic clefts and in preventing neuronal oxidative damage. Conversely, Dpl is expressed in heart and testis and has been shown to regulate male fertility by intervening in gametogenesis and sperm-egg interactions. Therefore, despite a high sequence homology and a similar three-dimensional fold, the functions of PrP(C) and Dpl appear unrelated. Here we show by electron paramagnetic resonance and fluorescence spectroscopy that the in vitro binding of copper(II) to human recombinant Dpl occurs with a different pattern from that observed for recombinant PrP. At physiological pH values, two copper(II)-binding sites with different affinities were found in Dpl. At lower pH values, two additional copper(II)-binding sites can be identified as follows: one complex is present only at pH 4, and the other is observed in the pH range 5-6. As derived from the electron paramagnetic resonance characteristics, all Dpl-c...Continue Reading

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Citations

Jun 14, 2005·Biochemical and Biophysical Research Communications·Akikazu SakudoTakashi Onodera
Aug 19, 2007·Physical Chemistry Chemical Physics : PCCP·Sabine Van Doorslaer, Evi Vinck
Mar 25, 2005·Molecular Biology of the Cell·Marisa BriniMaria Catia Sorgato
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Feb 25, 2009·Journal of Inorganic Biochemistry·Diego La MendolaEnrico Rizzarelli

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