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@ARTICLE{Owen:858916,
author = {Owen, Michael C. and Kulig, Waldemar and Poojari, Chetan
and Rog, Tomasz and Strodel, Birgit},
title = {{P}hysiologically-relevant levels of sphingomyelin, but not
{GM}1, induces a β-sheet-rich structure in the
amyloid-β(1-42) monomer},
journal = {Biochimica et biophysica acta / Biomembranes Biomembranes
[...]},
volume = {1860},
number = {9},
issn = {0005-2736},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {FZJ-2018-07752},
pages = {1709 - 1720},
year = {2018},
abstract = {To resolve the contribution of ceramide-containing lipids
to the aggregation of the amyloid-β protein into β-sheet
rich toxic oligomers, we employed molecular dynamics
simulations to study the effect of cholesterol-containing
bilayers comprised of POPC $(70\%$ POPC, and $30\%$
cholesterol) and physiologically relevant concentrations of
sphingomyelin (SM) $(30\%$ SM, $40\%$ POPC, and $30\%$
cholesterol), and the GM1 ganglioside $(5\%$ GM1, $70\%$
POPC, and $25\%$ cholesterol). The increased bilayer
rigidity provided by SM (and to a lesser degree, GM1)
reduced the interactions between the SM-enriched bilayer and
the N-terminus of Aβ42 (and also residues Ser26, Asn27, and
Lys28), which facilitated the formation of a β-sheet in the
normally disordered N-terminal region. Aβ42 remained
anchored to the SM-enriched bilayer through hydrogen bonds
with the side chain of Arg5. With β-sheets in the at the N
and C termini, the structure of Aβ42 in the
sphingomyelin-enriched bilayer most resembles β-sheet-rich
structures found in higher-ordered Aβ fibrils. Conversely,
when bound to a bilayer comprised of $5\%$ GM1, the
conformation remained similar to that observed in the
absence of GM1, with Aβ42 only making contact with one or
two GM1 molecules. This article is part of a Special Issue
entitled: Protein Aggregation and Misfolding at the Cell
Membrane Interface edited by Ayyalusamy Ramamoorthy.},
cin = {ICS-6},
ddc = {570},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {551 - Functional Macromolecules and Complexes (POF3-551)},
pid = {G:(DE-HGF)POF3-551},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29626441},
UT = {WOS:000442333600013},
doi = {10.1016/j.bbamem.2018.03.026},
url = {https://juser.fz-juelich.de/record/858916},
}