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@ARTICLE{Shaykhalishahi:279291,
author = {Shaykhalishahi, Hamed and Gauhar, Aziz and Wördehoff,
Michael M. and Grüning, Clara S. R. and Klein, Antonia N.
and Bannach, Oliver and Stoldt, Matthias and Willbold,
Dieter and Härd, Torleif and Hoyer, Wolfgang},
title = {{C}ontact between the β1 and β2 {S}egments of
α-{S}ynuclein that {I}nhibits {A}myloid {F}ormation},
journal = {Angewandte Chemie / International edition},
volume = {54},
number = {30},
issn = {1433-7851},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {FZJ-2015-07306},
pages = {8837 - 8840},
year = {2015},
abstract = {Conversion of the intrinsically disordered protein
α-synuclein (α-syn) into amyloid aggregates is a key
process in Parkinson’s disease. The sequence region
35–59 contains β-strand segments β1 and β2 of α-syn
amyloid fibril models and most disease-related mutations.
β1 and β2 frequently engage in transient interactions in
monomeric α-syn. The consequences of β1–β2 contacts are
evaluated by disulfide engineering, biophysical techniques,
and cell viability assays. The double-cysteine mutant
α-synCC, with a disulfide linking β1 and β2, is
aggregation-incompetent and inhibits aggregation and
toxicity of wild-type α-syn. We show that α-syn delays the
aggregation of amyloid-β peptide and islet amyloid
polypeptide involved in Alzheimer’s disease and type 2
diabetes, an effect enhanced in the α-synCC mutant.
Tertiary interactions in the β1–β2 region of α-syn
interfere with the nucleation of amyloid formation,
suggesting promotion of such interactions as a potential
therapeutic approach.},
cin = {ICS-6},
ddc = {540},
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},
UT = {WOS:000358051600050},
pubmed = {pmid:26119103},
doi = {10.1002/anie.201503018},
url = {https://juser.fz-juelich.de/record/279291},
}