Impact of Cu(ii) and Al(iii) on the conformational landscape of amyloidβ1-42
- 10 May 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Physical Chemistry Chemical Physics
- Vol. 23 (23), 13023-13032
- https://doi.org/10.1039/d1cp01561c
Abstract
Metal ions have been found to play an important role in the formation of extracellular β-amyloid plaques, a major hallmark of Alzheimer's disease. In the present study, the conformational landscape of Aβ42 with Al(III) and Cu(II) has been explored using Gaussian accelerated molecular dynamics. Both metals reduce the flexibility of the peptide and entail a higher structural organization, although to different degrees. As a general trend, Cu(II) binding leads to an increased α-helix content and to the formation of two α-helices that tend to organize in a U-shape. By contrast, most Al(III) complexes induce a decrease in helical content, leading to more extended structures that favor the appearance of transitory β-strands.Funding Information
- Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya (2017SGR1323, 2020FI_B2_01000)
- Secretaría de Estado de Investigación, Desarrollo e Innovación (RED2018-102471-T, CTQ2014-59544-P, CTQ2015-65439-R, CTQ2017-87889-P)
This publication has 59 references indexed in Scilit:
- Bioinorganic Chemistry of Alzheimer’s DiseaseChemical Reviews, 2012
- A partially folded structure of amyloid-beta(1–40) in an aqueous environmentBiochemical and Biophysical Research Communications, 2011
- The Heterogeneous Nature of Cu2+Interactions with Alzheimer’s Amyloid-β PeptideAccounts of Chemical Research, 2011
- Design of small molecules that target metal-Aβ species and regulate metal-induced Aβ aggregation and neurotoxicityProceedings of the National Academy of Sciences of the United States of America, 2010
- Amyloid-β Peptide Disruption of Lipid Membranes and the Effect of Metal IonsJournal of Molecular Biology, 2006
- Development and validation of a genetic algorithm for flexible dockingJournal of Molecular Biology, 1997
- A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP modelThe Journal of Physical Chemistry, 1993
- An interaction of β‐amyloid with aluminium in vitroFEBS Letters, 1993
- Langevin dynamics of peptides: The frictional dependence of isomerization rates of N‐acetylalanyl‐N′‐methylamidePeptide Science, 1992
- Comparison of simple potential functions for simulating liquid waterThe Journal of Chemical Physics, 1983