Journal article
A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding
M Mital, NE Wezynfeld, T Frączyk, MZ Wiloch, UE Wawrzyniak, A Bonna, C Tumpach, KJ Barnham, CL Haigh, W Bal, SC Drew
Angewandte Chemie International Edition | WILEY-V C H VERLAG GMBH | Published : 2015
Abstract
Accumulation of the β-amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer′s disease (AD). The Aβ1-x (x=16/28/40/42) peptides have been the primary focus of CuII binding studies for more than 15 years; however, the N-truncated Aβ4-42 peptide is a major Aβ isoform detected in both healthy and diseased brains, and it contains a novel N-terminal FRH sequence. Proteins with His at the third position are known to bind CuII avidly, with conditional log K values at pH 7.4 in the range of 11.0-14.6, which is much higher than that determined for Aβ1-x peptides. By using Aβ4-16 as a model, it was demonstrated that its FRH sequence..
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Grants
Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by a Future Fellowship (FT110100199) administered by the Australian Research Council (ARC) to S.C.D, an ARC Linkage Infrastructure, Equipment and Facilities grant (LE130100061) to S.C.D. and K.J.B., and a Senior Research Fellowship administered by the National Health and Medical Research Council of Australia to K.J.B. This work was also supported by the Foundation for Polish Science TEAM Program, co-financed from European Regional Development Fund resources within the framework of Operational Program Innovative Economy under the project "Metal-Dependent Peptide Hydrolysis Tools and Mechanisms for Biotechnology, Toxicology and Supramolecular Chemistry" (TEAM 2009-4/1) to W.B. The study was sponsored in part by the National Science Centre of Poland, grant no. 2014/15/B/ST5/05229. The equipment used was sponsored in part by the Centre for Preclinical Research and Technology (CePT), a project cosponsored by the European Regional Development Fund and Innovative Economy, The National Cohesion Strategy of Poland. Electrochemical studies were financially supported by the National Science Center of Poland SONATA project 2012/07/D/ST4/02187.