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@ARTICLE{Samantray:902427,
author = {Samantray, Suman and Strodel, Birgit},
title = {{T}he {E}ffects of {D}ifferent {G}lycosaminoglycans on the
{S}tructure and {A}ggregation of the {A}myloid-β (16–22)
{P}eptide},
journal = {The journal of physical chemistry / B},
volume = {125},
number = {21},
issn = {1089-5647},
address = {Washington, DC},
publisher = {Soc.},
reportid = {FZJ-2021-04249},
pages = {5511 - 5525},
year = {2021},
note = {Kein Post-print vorhanden!},
abstract = {Aggregates of the amyloid-β (Aβ) peptide are implicated
as a causative substance in Alzheimer’s disease. Molecular
dynamics simulations provide valuable contributions for
elucidating the conformational transitions of monomeric and
aggregated forms of Aβ be it in solution or in the presence
of other molecules. Here, we study the effects of four
different glycosaminoglycans (GAGs), three sulfated ones and
a nonsulfated one, on the aggregation of Aβ16–22. From
experiments, it has been suggested that GAGs, which belong
to the main components of the brain’s extracellular space,
favor amyloid fibril formation. Our simulation results
reveal that the binding of Aβ16–22 to the GAGs is driven
by electrostatic attraction between the negative GAG charges
and the positively charged K16 of Aβ16–22. While these
interactions have only minor effects on the GAG and
Aβ16–22 conformations at the 1 Aβ16–22/1 GAG ratio, at
the 2:2 stoichiometry the aggregation of Aβ16–22 is
considerably changed. In solution, the aggregation of
Aβ16–22 is strongly influenced by K16–E22 attraction,
leading to antiparallel β-sheets. In the presence of GAGs,
on the other hand, the interaction of K16 with the GAGs
increases the importance of the hydrophobic interactions
during Aβ16–22 aggregation, which in turn yields parallel
alignments. A templating and ordering effect of the GAGs on
the Aβ16–22 aggregates is observed. In summary, this
study provides new insight at the atomic level on
GAG–amyloid interactions, strengthening the view that
sulfation of the GAGs plays a major role in this context.},
cin = {IBI-7},
ddc = {530},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {34027669},
UT = {WOS:000661116600007},
doi = {10.1021/acs.jpcb.1c00868},
url = {https://juser.fz-juelich.de/record/902427},
}