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@ARTICLE{Yang:841860,
author = {Yang, Ge and Yu, Kun and Kaitatzi, Christina-Symina and
Singh, Abhilasha and Labahn, Jörg},
title = {{I}nfluence of solubilization and {AD}-mutations on
stability and structure of human presenilins},
journal = {Scientific reports},
volume = {7},
number = {1},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2018-00157},
pages = {17970},
year = {2017},
abstract = {Presenilin (PS1 or PS2) functions as the catalytic subunit
of γ-secretase, which produces the toxic amyloid beta
peptides in Alzheimer’s disease (AD). The dependence of
folding and structural stability of PSs on the lipophilic
environment and mutation were investigated by far UV CD
spectroscopy. The secondary structure content and stability
of PS2 depended on the lipophilic environment. PS2 undergoes
a temperature-dependent structural transition from
α-helical to β-structure at 331 K. The restructured
protein formed structures which tested positive in
spectroscopic amyloid fibrils assays. The AD mutant
PS1L266F, PS1L424V and PS1ΔE9 displayed reduced stability
which supports a proposed ‘loss of function’ mechanism
of AD based on protein instability. The exon 9 coded
sequence in the inhibitory loop of the zymogen was found to
be required for the modulation of the thermal stability of
PS1 by the lipophilic environment.},
cin = {ICS-6},
ddc = {000},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29269939},
UT = {WOS:000418562100010},
doi = {10.1038/s41598-017-18313-x},
url = {https://juser.fz-juelich.de/record/841860},
}