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@ARTICLE{Fatafta:902425,
author = {Fatafta, Hebah and Kav, Batuhan and Bundschuh, Bastian F.
and Loschwitz, Jennifer and Strodel, Birgit},
title = {{D}isorder-to-order transition of the amyloid-β peptide
upon lipid binding},
journal = {Biophysical chemistry},
volume = {280},
issn = {0301-4622},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2021-04247},
pages = {106700 -},
year = {2022},
abstract = {There is mounting evidence that Alzheimer's disease
progression and severity are linked to neuronal membrane
damage caused by aggregates of the amyloid- (A) peptide.
However, the detailed mechanism behind the membrane damage
is not well understood yet. Recently, the lipid-chaperone
hypothesis has been put forward, based on which the
formation of complexes between A and free lipids enables an
easy insertion of A into membranes. In order to test this
hypothesis, we performed numerous all-atom molecular
dynamics simulations. We studied the complex formation
between individual lipids, considering both POPC and DPPC,
and A and examined whether the resulting complexes would be
able to insert into lipid membranes. Complex formation at a
one-to-one ratio was readily observed, yet with minimal
effects on A's characteristics. Most importantly, the
peptide remains largely disordered in 1:1 complexes, and the
complex does not insert into the membrane; instead, it is
adsorbed to the membrane surface. The results change
considerably once A forms a complex with a POPC cluster
composed of three lipid molecules. The hydrophobic
interactions between A and the lipid tails cause the peptide
to fold into either a helical or a -sheet structure. These
observations provide atomic insight into the
disorder-to-order transition that is needed for membrane
insertion or amyloid aggregation to proceed.},
cin = {IBI-7},
ddc = {540},
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 = {34784548},
UT = {WOS:000722063800001},
doi = {10.1016/j.bpc.2021.106700},
url = {https://juser.fz-juelich.de/record/902425},
}