Pulse EPR Spectroscopy Reveals the Coordination Sphere of Copper(II) Ions in the 1–16 Amyloid-β Peptide: A Key Role of the First Two N-Terminus Residues

Authors

  • Pierre Dorlet Dr.,

    1. CNRS, Laboratoire du Stress Oxydant et Détoxication, URA 2096, 91191 Gif-sur-Yvette (France)
    2. CEA, iBiTec-S, SB2SM, 91191 Gif-sur-Yvette (France), Fax: (+33) 169-088-717
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  • Serge Gambarelli Dr.,

    1. CEA, Laboratoire de Résonance Magnétique, INAC/SCIB, UMR E3 CEA-UJF, 17, rue des Martyrs, 38054 Grenoble Cedex 9 (France)
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  • Peter Faller Prof.,

    1. CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, 31077 Toulouse (France)
    2. Université de Toulouse, UPS, INPT, LCC, 31077 Toulouse (France)
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  • Christelle Hureau Dr.

    1. CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, 31077 Toulouse (France)
    2. Université de Toulouse, UPS, INPT, LCC, 31077 Toulouse (France)
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  • This work was supported by ANR grants 05-JCJC-0010-01 “NEUROARPE” (P.D.) and NT09-488591 “NEUROMETALS” (P.F., P.D.)

Abstract

original image

Ligand sphere revealed: Cu ions were proposed to be linked to the aggregation of the amyloid-β peptide in Alzheimer's disease. However, unambiguous identification of the Cu ligands has remained difficult. The use of various EPR spectroscopies with specific isotopic labeling now allowed the assignment of the CuII ligands for both complexes present at physiological pH value (see 3D plots and structures). The results indicate that the peptide's first two amino acids are important for coordination and probably aggregation.

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