Multi-Frequency, Multi-Technique Pulsed EPR Investigation of the Copper Binding Site of Murine Amyloid β Peptide

Copper‐amyloid peptides are proposed to be the cause of Alzheimer’s disease, presumably by oxidative stress. However, mice do not produce amyloid plaques and thus do not suffer from Alzheimer’s disease. Although much effort has been focused on the structural characterization of the copper‐ human amy...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2015-01, Vol.54 (5), p.1561-1564
Main Authors: Kim, Donghun, Bang, Jeong Kyu, Kim, Sun Hee
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - metabolism
Animals
Binding Sites
Copper
Copper - chemistry
Copper - metabolism
Electron Spin Resonance Spectroscopy
ENDOR
EPR spectroscopy
Hydrogen-Ion Concentration
HYSCORE
Inhibitors
Isotopes
Marking
Mice
murine amyloid peptides
Peptides
Protein Binding
Spectroscopy
Structural analysis
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Summary:Copper‐amyloid peptides are proposed to be the cause of Alzheimer’s disease, presumably by oxidative stress. However, mice do not produce amyloid plaques and thus do not suffer from Alzheimer’s disease. Although much effort has been focused on the structural characterization of the copper‐ human amyloid peptides, little is known regarding the copper‐binding mode in murine amyloid peptides. Thus, we investigated the structure of copper‐murine amyloid peptides through multi‐frequency, multi‐technique pulsed EPR spectroscopy in conjunction with specific isotope labeling. Based on our pulsed EPR results, we found that Ala2, Glu3, His6, and His14 are directly coordinated with the copper ion in murine amyloid β peptides at pH 8.5. This is the first detailed structural characterization of the copper‐binding mode in murine amyloid β peptides. This work may advance the knowledge required for developing inhibitors of Alzheimer’s disease. Pulsed EPR spectroscopy in conjunction with specific isotope labeling was employed to investigate the structure of copper‐murine amyloid peptides. This first detailed structural characterization shows that Ala2, Glu3, His6, and His14 are directly coordinated with the copper ion in murine amyloid β peptides at pH 8.5.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201410389