Journal article

The Human Amyloid Precursor Protein Binds Copper Ions Dominated by a Picomolar-Affinity Site in the Helix-Rich E2 Domain

Tessa R Young, Tara L Pukala, Roberto Cappai, Anthony G Wedd, Zhiguang Xiao

BIOCHEMISTRY | AMER CHEMICAL SOC | Published : 2018

Abstract

A manifestation of Alzheimer's disease (AD) is the aggregation in the brain of amyloid β (Aβ) peptides derived from the amyloid precursor protein (APP). APP has been linked to modulation of normal copper homeostasis, while dysregulation of Aβ production and clearance has been associated with disruption of copper balance. However, quantitative copper chemistry on APP is lacking, in contrast to the plethora of copper chemistry available for Aβ peptides. The soluble extracellular protein domain sAPPα (molar mass including post-translational modifications of ∼100 kDa) has now been isolated in good yield and high quality. It is known to feature several copper binding sites with different affiniti..

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Grants

Awarded by Australian Research Council


Funding Acknowledgements

This work was supported by funds from Australian Research Council Grant DP130100728. Additional financial support for T.R.Y. was generously provided by the Norma Hilda Schuster (nee Swift) Scholarship Fund and the Albert Shimmins Fund.