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@ARTICLE{Mirecka:821077,
author = {Mirecka, Ewa A. and Feuerstein, Sophie and Gremer, Lothar
and Schröder, Gunnar F. and Stoldt, Matthias and Willbold,
Dieter and Hoyer, Wolfgang},
title = {β-{H}airpin of {I}slet {A}myloid {P}olypeptide {B}ound to
an {A}ggregation {I}nhibitor},
journal = {Scientific reports},
volume = {6},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2016-06321},
pages = {33474 -},
year = {2016},
abstract = {In type 2 diabetes, the formation of islet amyloid
consisting of islet amyloid polypeptide (IAPP) isassociated
with reduction in β-cell mass and contributes to the
failure of islet cell transplantation.Rational design of
inhibitors of IAPP amyloid formation has therapeutic
potential, but is hampered bythe lack of structural
information on inhibitor complexes of the conformationally
flexible, aggregationproneIAPP. Here we characterize a
β-hairpin conformation of IAPP in complex with the
engineeredbinding protein β-wrapin HI18. The β-strands
correspond to two amyloidogenic motifs, 12-LANFLVH-18and
22-NFGAILS-28, which are connected by a turn established
around Ser-20. Besides backbonehydrogen bonding, the
IAPP:HI18 interaction surface is dominated by non-polar
contacts involvinghydrophobic side chains of the IAPP
β-strands. Apart from monomers, HI18 binds oligomers and
fibrilsand inhibits IAPP aggregation and toxicity at low
substoichiometric concentrations. The IAPP β-hairpincan
serve as a molecular recognition motif enabling control of
IAPP aggregation.},
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},
UT = {WOS:000383383100001},
pubmed = {pmid:27641459},
doi = {10.1038/srep33474},
url = {https://juser.fz-juelich.de/record/821077},
}