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@ARTICLE{Palomino:878039,
author = {Palomino, Oscar and Buratti, Fiamma A. and Sacco, Pamela S.
and Rossetti, Giulia and Carloni, Paolo and Fernandez,
Claudio O.},
title = {{R}ole of {T}yr-39 for the {S}tructural {F}eatures of
α-{S}ynuclein and for the {I}nteraction with a {S}trong
{M}odulator of {I}ts {A}myloid {A}ssembly},
journal = {International journal of molecular sciences},
volume = {21},
number = {14},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2020-02595},
pages = {5061 -},
year = {2020},
abstract = {Recent studies suggest that Tyr-39 might play a critical
role for both the normal function and the pathological
dysfunction of α-synuclein (αS), an intrinsically
disordered protein involved in Parkinson’s disease. We
perform here a comparative analysis between the structural
features of human αS and its Y39A, Y39F, and Y39L variants.
By the combined application of site-directed mutagenesis,
biophysical techniques, and enhanced sampling molecular
simulations, we show that removing aromatic functionality at
position 39 of monomeric αS leads to protein variants
populating more compact conformations, conserving its
disordered nature and secondary structure propensities.
Contrasting with the subtle changes induced by mutations on
the protein structure, removing aromaticity at position 39
impacts strongly on the interaction of αS with the potent
amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our
findings further support the role of Tyr-39 in forming
essential inter and intramolecular contacts that might have
important repercussions for the function and the dysfunction
of αS.},
cin = {INM-11 / JSC / INM-9 / IAS-5 / JARA-HPC},
ddc = {540},
cid = {I:(DE-Juel1)INM-11-20170113 / I:(DE-Juel1)JSC-20090406 /
I:(DE-Juel1)INM-9-20140121 / I:(DE-Juel1)IAS-5-20120330 /
$I:(DE-82)080012_20140620$},
pnm = {511 - Computational Science and Mathematical Methods
(POF3-511) / Exploring the conformational properties of
alpha-synuclein variants: an enhanced sampling study
$(jara0209_20200501)$},
pid = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)jara0209_20200501$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32709107},
UT = {WOS:000554212600001},
doi = {10.3390/ijms21145061},
url = {https://juser.fz-juelich.de/record/878039},
}