Copper(II)‐bis‐Histidine Coordination Structure in a Fibrillar Amyloid β‐Peptide Fragment and Model Complexes Revealed by Electron Spin Echo Envelope Modulation Spectroscopy |
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Authors: | Dr Jessica Hernández‐Guzmán Dr Li Sun Dr Anil K Mehta Dr Jijun Dong Prof David G Lynn Prof Kurt Warncke |
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Affiliation: | 1. Department of Physics, Emory University, Atlanta, GA 30322‐2430 (USA);2. Department of Chemistry, Emory University, Atlanta, GA 30322‐2430 (USA) |
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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. |
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Keywords: | amyloid beta‐peptides bioinorganic chemistry copper EPR spectroscopy ESEEM spectroscopy |
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