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Folding of the prion peptide GGGTHSQW around the copper(II) ion: identifying the oxygen donor ligand at neutral pH and probing the proximity of the tryptophan residue to the copper ion

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Abstract

The GGGTHSQW sequence in the amyloidogenic part of the prion protein is a potential binding site for Cu(II). We have previously studied the binding of copper to the shorter GGGTH peptide and showed that it is highly pH dependent (Hureau et al. in J. Biol. Inorg. Chem. 11:735–744, 2006). Two predominant complexes could be characterized at pH 6.7 and 9.0 with equatorial binding modes of 3N1O and 4N for the metal ion, respectively. In this work, we have further investigated the coordination of Cu(II) to the GGGTH peptide as well as the longer GGGTHSQW peptide in order to identify the oxygen donor ligand at neutral pH and to study the proximity and redox activity of the tryptophan residue of the latter. The results for both peptides show that, at pH 6.7, Cu(II) is coordinated by a carbonyl peptide backbone. At higher pH values, the carbonyl ligand dissociates and the coordination changes to a 4N binding mode, inducing a structural rearrangement that brings the GGGTHSQW peptide’s tryptophan residue into the vicinity of the copper ion, thus affecting their respective redox properties.

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Abbreviations

ATR:

Attenuated total reflection

ENDOR:

Electron–nuclear double resonance

EPR:

Electron paramagnetic resonance

ESEEM:

Electron spin echo envelope modulation

FTIR:

Fourier transform infrared

HYSCORE:

Hyperfine sublevel correlation

P5:

Ac–GGGTH–NH2

P8:

Ac–GGGTHSQW–NH2

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Acknowledgments

This work was supported by a grant from the Agence Nationale de la Recherche, Programme Jeunes Chercheuses Jeunes Chercheurs (ANR-05-JCJC-0010 ‘NEUROARPE’ to P.D., including a postdoctoral fellowship to C.M.). We thank Guillaume Blain for technical assistance and maintenance of the Elexys EPR/ENDOR spectrometer, Emmanuelle Mothes and Luc Guilloreau for fluorescence measurements, Jérôme Santolini for assistance with the ATR-FTIR measurements, Alain Boussac for the use of the pulsed-EPR spectrometer and Elodie Anxolabéhère-Mallart for discussions.

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Authors and Affiliations

  1. Laboratoire du Stress Oxydant et Détoxication, CNRS URA 2096, iBiTec-S, CEA Saclay, 91191, Gif-sur-Yvette Cedex, France

    Tony A. Mattioli & Pierre Dorlet

  2. Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS UMR 8182, Equipe de Chimie Inorganique, Université Paris-Sud, 91405, Orsay Cedex, France

    Christelle Hureau, Christelle Mathé & Pierre Dorlet

  3. Laboratoire de Chimie de Coordination, CNRS UPR 8241, 205, route de Narbonne, 31077, Toulouse Cedex, France

    Christelle Hureau & Peter Faller

Authors
  1. Christelle Hureau
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  2. Christelle Mathé
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  3. Peter Faller
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  4. Tony A. Mattioli
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  5. Pierre Dorlet
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Correspondence to Pierre Dorlet.

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Hureau, C., Mathé, C., Faller, P. et al. Folding of the prion peptide GGGTHSQW around the copper(II) ion: identifying the oxygen donor ligand at neutral pH and probing the proximity of the tryptophan residue to the copper ion. J Biol Inorg Chem 13, 1055–1064 (2008). https://doi.org/10.1007/s00775-008-0389-0

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