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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Israel Journal of Ch...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Israel Journal of Chemistry
Article . 2017 . Peer-reviewed
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Conformational Transitions of the Amyloid‐β Peptide Upon Copper(II) Binding and pH Changes

Authors: Olujide O. Olubiyi; Qinghua Liao; Bogdan Barz; Bogdan Barz; Birgit Strodel; Birgit Strodel; Michael C. Owen;

Conformational Transitions of the Amyloid‐β Peptide Upon Copper(II) Binding and pH Changes

Abstract

AbstractAmyloid‐β (Aβ) is a natively unfolded peptide found in all Alzheimer's disease patients as the major component of fibrillar plaques, which are recognized as an important pathological hallmark in Alzheimer's disease. The binding of copper to Aβ increases its neurotoxicity, as Cu2+causes Aβ to become redox active and decreases the lag time associated with Aβ aggregation. In addition, the pH is a major factor that influences both the Aβ aggregation rates and Cu2+binding. Hamiltonian replica exchange molecular dynamics (H‐REMD) simulations enable atomistic insights into the effects of pH and Cu2+complexation on the structure and dynamics of Aβ. To study the Aβ1–42/Cu2+complex, we have developed new force‐field parameters for the divalent copper ion ligated by the two histidine residues, His6 and His13, as well as the amine and carbonyl groups of Asp1, in a distorted square‐planar geometry. Our comparative simulations reveal that both Cu2+binding and a low pH‐mimicking acidosis, linked to inflammatory processes in vivo, accelerate the formation of β‐strands in Aβ1–42and lead to the stabilization of salt bridges, previously shown to promote Aβ aggregation. The results suggest that Cu2+binding and mild acidic conditions can shift the conformational equilibrium towards aggregation‐prone conformers for the monomeric Aβ.

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    22
    popularity
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    Top 10%
    influence
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Average
Top 10%