A spectroscopic and voltammetric study of the pH-dependent Cu(II) coordination to the peptide GGGTH: relevance to the fifth Cu(II) site in the prion protein

The GGGTH sequence has been proposed to be the minimal sequence involved in the binding of a fifth Cu(II) ion in addition to the octarepeat region of the prion protein (PrP) which binds four Cu(II) ions. Coordination of Cu(II) by the N- and C-protected Ac-GGGTH-NH(2) pentapeptide (P(5)) was investig...

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Bibliographic Details
Published in:Journal of biological inorganic chemistry 2006-09, Vol.11 (6), p.735-744
Main Authors: Hureau, Christelle, Charlet, Laurent, Dorlet, Pierre, Gonnet, Florence, Spadini, Lorenzo, Anxolabéhère-Mallart, Elodie, Girerd, Jean-Jacques
Format: Article
Language:English
Subjects:
Copper - chemistry
Electron Spin Resonance Spectroscopy
Hydrogen-Ion Concentration
Mathematics
Oligopeptides - chemistry
Potentiometry
Prions - chemistry
Spectral Theory
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
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Summary:The GGGTH sequence has been proposed to be the minimal sequence involved in the binding of a fifth Cu(II) ion in addition to the octarepeat region of the prion protein (PrP) which binds four Cu(II) ions. Coordination of Cu(II) by the N- and C-protected Ac-GGGTH-NH(2) pentapeptide (P(5)) was investigated by using potentiometric titration, electrospray ionization mass spectrometry, UV-vis spectroscopy, electron paramagnetic resonance (EPR) spectroscopy and cyclic voltammetry experiments. Four different Cu(II) complexes were identified and characterized as a function of pH. The Cu(II) binding mode switches from NO(3) to N(4) for pH values ranging from 6.0 to 10.0. Quasi-reversible reduction of the [Cu(II)(P(5))H(-2)] complex formed at pH 6.7 occurs at E (1/2)=0.04 V versus Ag/AgCl, whereas reversible oxidation of the [Cu(II)(P(5))H(-3)](-) complex formed at pH 10.0 occurs at E (1/2)=0.66 V versus Ag/AgCl. Comparison of our EPR data with those of the rSHaPrP(90-231) (Burns et al. in Biochemistry 42:6794-6803, 2003) strongly suggests an N(3)O binding mode at physiological pH for the fifth Cu(II) site in the protein.
ISSN:0949-8257
1432-1327
DOI:10.1007/s00775-006-0118-5