Kinetics of the Interactions between Copper and Amyloid-β with FAD Mutations and Phosphorylation at the N-terminus
File(s)
Published version
Supporting information
Author(s)
Girvan, P
Miyake, T
Teng, X
Branch, T
Ying, L
Type
Journal Article
Abstract
Mutations and post-translational modifications of amyloid-β (Aβ) peptide in its N terminus have been shown to increase fibril formation, yet the molecular mechanism is not clear. Here we investigated the kinetics of the interactions of copper with two Aβ peptides containing Familial Alzheimer's disease (FAD) mutations (English (H6R) and Tottori (D7N)), as well as with Aβ peptide phosphorylated at serine 8 (pS8). All three peptides bind to copper with a similar rate as the wild-type (wt). The dissociation rates follow the order pS8>H6R>wt>D7N; the interconversion between the two coordinating species occurs 50 % faster for H6R and pS8, whereas D7N had only a negligible effect. Interestingly, the rate of ternary complex (copper-bridged heterodimer) formation for the modified peptides was significantly faster than that for wt, thus leading us to propose that FAD and sporadic AD might share a kinetic origin for the enhanced oligomerisation of Aβ.
Date Issued
2016-08-02
Date Acceptance
2016-06-27
Citation
Chembiochem, 2016, 17 (18), pp.1732-1737
ISSN
1439-7633
Publisher
Wiley-VCH Verlag
Start Page
1732
End Page
1737
Journal / Book Title
Chembiochem
Volume
17
Issue
18
Copyright Statement
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution
License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution
License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
License URL
Subjects
amyloid beta-peptides
copper
fluorescence spectroscopy
kinetics
reaction mechanism
Organic Chemistry
0304 Medicinal And Biomolecular Chemistry
0601 Biochemistry And Cell Biology
Publication Status
Published