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Author Notes:

Kurt Warncke: kwarncke@physics.emory.edu.

Subjects:

Research Funding:

This work was supported, in part, by an Emory University Arts and Sciences Partnership Seed Funding Program grant.

The authors acknowledge the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U.S. Department of Energy through Grant DEER15377 for peptide synthesis and analyses.

Research reported in this publication was supported, in part, by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01 DK054514.

The purchase of the Bruker E500 EPR spectrometer was funded by National Institutes of Health, National Center for Research Resources grant RR17767, and by Emory University.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Chemistry, Medicinal
  • Pharmacology & Pharmacy
  • amyloid beta-peptides
  • bioinorganic chemistry
  • copper
  • EPR spectroscopy
  • ESEEM spectroscopy
  • ALZHEIMERS-DISEASE
  • PRION PROTEIN
  • COPPER(II) BINDING
  • ALPHA-SYNUCLEIN
  • POWDER SPECTRA
  • CU2+ BINDING
  • CU(II)
  • IMIDAZOLE
  • ESEEM
  • ZINC

Copper(II)-bis-Histidine Coordination Structure in a Fibrillar Amyloid beta-Peptide Fragment and Model Complexes Revealed by Electron Spin Echo Envelope Modulation Spectroscopy

Tools:

Journal Title:

ChemBioChem

Volume:

Volume 14, Number 14

Publisher:

, Pages 1762-1771

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Truncated and mutated amyloid-β (Aβ) peptides are models for systematic study-in homogeneous preparations-of the molecular origins of metal ion effects on Aβ aggregation rates, types of aggregate structures formed, and cytotoxicity. The 3D geometry of bis-histidine imidazole coordination of CuII in fibrils of the nonapetide acetyl-Aβ(13-21)H14A has been determined by powder 14N electron spin echo envelope modulation (ESEEM) spectroscopy. The method of simulation of the anisotropic combination modulation is described and benchmarked for a CuII-bis-cis-imidazole complex of known structure. The revealed bis-cis coordination mode, and the mutual orientation of the imidazole rings, for CuII in Ac-Aβ(13-21)H14A fibrils are consistent with the proposed β-sheet structural model and pairwise peptide interaction with CuII, with an alternating [-metal-vacancy-]n pattern, along the N-terminal edge. Metal coordination does not significantly distort the intra-β-strand peptide interactions, which provides a possible explanation for the acceleration of Ac-Aβ(13-21)H14A fibrillization by CuII, through stabilization of the associated state and low-reorganization integration of β-strand peptide pair precursors.

Copyright information:

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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