Object's details: A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding
Creator:
Mital, Mariusz;
Wezynfeld, Nina Ewa;
Frączyk, Tomasz;
Wiloch, Magdalena;
Wawrzyniak, Urszula;
Bonna, Arkadiusz;
Tumpach, Carolin;
Barnham, Kevin;
Haigh, Cathryn;
Bal, Wojciech;
Drew, Simon
Description:
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 Cu(II) 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 Cu(II) 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 stoichiometrically binds Cu(II) with a conditional Kd value of 3×10(-14) M at pH 7.4, and that both Aβ4-16 and Aβ4-42 possess negligible redox activity. Combined with the predominance of Aβ4-42 in the brain, our results suggest a physiological role for this isoform in metal homeostasis within the central nervous system.
Object availability:
free access
Date:
2015.07.14
Type:
Article;
PeerReviewed
Publisher:
Wiley-VCH
Relation: http://eprints.ibb.waw.pl/1078 ;http://onlinelibrary.wiley.com/doi/10.1002/anie.201502644/abstract
Subject:
QD Chemistry;
QH301 Biology;
RB Pathology
Identifier:
Mital, Mariusz and Wezynfeld, Nina Ewa and Frączyk, Tomasz and Wiloch, Magdalena and Wawrzyniak, Urszula and Bonna, Arkadiusz and Tumpach, Carolin and Barnham, Kevin and Haigh, Cathryn and Bal, Wojciech and Drew, Simon (2015) A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding. Angewandte Chemie International Edition, 54 . pp. 10460-10464. ISSN 1521-3773
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding

Description

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