ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
O6. Electron Paramagnetic Resonance Studies of Copper Binding Sites in
Peptides Related to Neurodegenerative Diseases
P. Dorlet a , C. Hureau b , P. Faller c
a URA 2096- iBiTecS, CNRS, Bat 532 CEA Saclay, 91191, Gif-sur-Yvette, France
b UPR 824, CNRS, 205 Route de Narbonne, 31077, Toulouse, France
c CNRS UPR 8241, Universite Paul-Sabatier, 205 route de Narbonne, 31077, Toulouse, France
The Prion Protein (PrP) and the amyloid-b peptide (Ab) are involved in transmissible spongiform
encephalopathies and Alzheimer's disease, respectively, which are fatal neurodegenerative disorders.
We have recently investigated the Cu(II) coordination to the N- and C-protected Ac-GGGTH-NH2 and
Ac-GGGTHSQW-NH2 peptides [1, 2] as models of the His96 site in PrP, one of the proposed non-octarepeat Cu
binding sites [3]. We have shown that, at pH 6.7, the Cu(II) coordination mode is 3N1O in the peptides. The
binding mode becomes quantitatively 4N at pH higher than 8. At physiological pH (7.5), comparison of the EPR
spectra obtained on the peptides with that recorded on the PrP protein by Burns and coworkers [3] suggests a
3N1O binding mode in the protein [1] whereas a roughly 1:1 mixture of 3N1O and 4N coordination modes is
encountered for the peptides [2] in agreement with the previous study of Burns [3].
Concerning the Cu(II) coordination to the histidine-rich Ab peptide, there is yet no real coC Hureau, nsensus in
the literature [4, 5]. We are currently working on the coordination of Cu(II) to the Ab16 peptide
DAEFRHDSGYEVHHQK, the hydrophilic domain of the Ab peptide that contains all the ligands of the Cu(II)
ion. We are using advanced EPR techniques in combination to specific amino-acid labeling in order to identify
unambiguously the coordination sphere of the Cu(II) ion as a function of pH.
References:
[1] C. Hureau, L. Charlet, P. Dorlet, F. Gonnet, L. Spadini, E. Anxolabéhère-Mallart, J.-J. Girerd J. Biol. Inorg.
Chem. 2006, 11, 735-744
[2] C. Hureau, C. Mathé, P. Faller, T. A. Mattioli, P. Dorlet J. Biol. Inorg. Chem. 2008, in press
[3] C. S. Burns, E. Aronoff-Spencer, G. Legname, S. B. Prusiner, W. E. Antholine, G. J. Gerfen, J. Peisach, G.
Millhauser, Biochemistry 2003, 42, 6794-6803
[4] E. Gaggelli, H. Kozlowski, D. Valensin, G. Valensin, Chem. Rev. 2006, 106, 1995-2044
[5] C. Hureau, P. Faller, in preparation
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