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α-Synuclein and β-Amyloid form a Bridged Copper Complex

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Abstract

The deposition of insoluble β-amyloid (Aβ) peptide into extracellular senile plaques is a pathological hallmark of Alzheimer’s disease. Fragmented α-synuclein (αSyn) and a relatively high concentration of Cu2+ ions are found within amyloid deposits. Both Aβ and αSyn bind Cu2+ with an apparent dissociation constant in the sub-nanomolar range at physiological pH, fuelling speculation that deleterious redox chemistry and metal-mediated protein misfolding may contribute to disease progression. Binary Cu(Aβ) and Cu(αSyn) complexes have been extensively studied, although the Cu2+ coordination of heterogeneous mixtures of Aβ and αSyn has yet to be characterised. This study used synthetic N-terminal fragments Aβ1–16 and αSyn1–56 to reveal a new Cu(αSyn)(Aβ) coordination mode anchored upon a 5,6-membered chelate supplied by Met1–Asp2 of αSyn, with the fourth equatorial ligand being supplied by a His side chain of Aβ.

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Acknowledgments

This work was funded by a Fellowship (FT110100199) administered by the Australian Research Council.

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Authors and Affiliations

  1. Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia

    Simon C. Drew

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  1. Simon C. Drew
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Correspondence to Simon C. Drew.

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Drew, S.C. α-Synuclein and β-Amyloid form a Bridged Copper Complex. Appl Magn Reson 46, 1041–1052 (2015). https://doi.org/10.1007/s00723-015-0662-7

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