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Related Experiment Videos

The PrP-like protein Doppel binds copper.

Kefeng Qin1, Janaky Coomaraswamy, Peter Mastrangelo

  • 1Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada.

The Journal of Biological Chemistry
|December 17, 2002
PubMed
Summary

The prion-related Doppel protein (Dpl) selectively binds copper (Cu(II)) in its alpha-helical region, influencing its function rather than causing oxidative damage.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Protein Chemistry

Background:

  • Doppel (Dpl) is a testis-expressed protein homologous to the prion protein (PrP).
  • Dpl lacks the octarepeat region crucial for PrP's copper binding.
  • The role of metal ions, particularly copper, in Dpl's function is largely unknown.

Purpose of the Study:

  • To investigate the potential for copper binding by the Doppel protein.
  • To characterize the binding site and affinity of copper for Dpl.
  • To assess the functional implications of copper binding on Dpl's activity and stability.

Main Methods:

  • Intrinsic fluorescence spectroscopy to detect copper-induced changes in Dpl.
  • Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) for peptide analysis.

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  • Diethylpyrocarbonate (DEPC) footprinting to identify copper-protected residues.

    • Main Results:

    • Copper(II) significantly quenched Dpl's intrinsic fluorescence, indicating binding.
    • Copper specifically bound to the alpha-helical region (alphaB/B'-loop-alphaC) of Dpl.
    • A submicromolar dissociation constant (K(d)) was determined for copper binding to Dpl peptides, suggesting high affinity.

    Conclusions:

    • The alpha-helical region of mouse Doppel protein possesses a selective, high-affinity copper-binding site.
    • Copper binding to Dpl likely modulates its activity, stability, or localization, not promoting oxidative damage.
    • Findings challenge previous assumptions about Dpl's role in protein carbonylation and nitrosylation.