% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Nath:1025423,
author = {Nath, Soumav and Buell, Alexander K. and Barz, Bogdan},
title = {{P}yroglutamate-modified amyloid β(3–42) monomer has
more β-sheet content than the amyloid β(1–42) monomer},
journal = {Physical chemistry, chemical physics},
volume = {25},
number = {24},
issn = {1463-9076},
address = {Cambridge},
publisher = {RSC Publ.},
reportid = {FZJ-2024-02882},
pages = {16483 - 16491},
year = {2023},
abstract = {The aggregation of the amyloid β (Aβ) peptide is a major
hallmark of Alzheimer's disease. This peptide can aggregate
into oligomers, proto-fibrils and mature fibrils, which
eventually assemble into amyloid plaques in vivo. Several
post-translational modifications lead to the presence of
different forms of the Aβ peptide in the amyloid plaques
with different biophysical and biochemical properties. While
the canonical forms Aβ(1–40) and Aβ(1–42) have been
found to be the major components of amyloid plaques,
N-terminally pyroglutamate-modified variants, specifically
pE-Aβ(3–42), amount to a significant fraction of the
total Aβ plaque content of AD brains. With increased
hydrophobicity, these variants display a more pronounced
aggregation behaviour in vitro which, together with their
higher stability against degradation in vivo is thought to
make them crucial molecular players in the aetiology of AD.
The peptide monomers are the smallest assembly units, and
play an important role in most of the individual molecular
processes involved in amyloid fibril formation, such as
primary and secondary nucleation and elongation.
Understanding the monomeric conformational ensembles of the
isoforms is important in unraveling observed differences in
their bio-physico-chemical properties. Here we use enhanced
and extensive molecular dynamics simulations to study the
structural flexibility of the N-terminally truncated
Pyroglutamate modified isomer of Aβ, pE-Aβ(3–42)
monomer, and compared it with simulations of the Aβ(1–42)
peptide monomer under the same conditions. We find
significant differences, especially in the secondary
structure and hydrophobic exposure, which might be
responsible for their different behaviour in biophysical
experiments.},
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 = {37306611},
UT = {WOS:001004437400001},
doi = {10.1039/D2CP05961D},
url = {https://juser.fz-juelich.de/record/1025423},
}