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@ARTICLE{Intze:279351,
author = {Intze, Antonia and Temperini, Maria Eleonora and Rupert,
Jakob and Polito, Raffaella and Veber, Alexander and Puskar,
Ljiljana and Schade, Ulrich and Ortolani, Michele and Zacco,
Elsa and Tartaglia, Gian Gaetano and Giliberti, Valeria},
title = {{E}ffect of {RNA} on the supramolecular architecture of
α-synuclein fibrils.},
journal = {Biophysical journal},
volume = {124},
number = {12},
issn = {0006-3495},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DZNE-2025-00728},
pages = {2005 - 2019},
year = {2025},
abstract = {Structural changes associated with protein aggregation are
challenging to study, requiring the combination of
experimental techniques providing insights at the molecular
level across diverse scales, ranging from nanometers to
microns. Understanding these changes is even more complex
when aggregation occurs in the presence of molecular
cofactors such as nucleic acids and when the resulting
aggregates are highly polymorphic. Infrared (IR)
spectroscopy is a powerful tool for studying protein
aggregates since it combines the label-free sensitivity to
the cross-β architecture, an inherent feature of protein
supramolecular aggregates, with the possibility to reach
nanoscale sensitivity by leveraging atomic force microscopy
(AFM)-assisted detection. Here, we present a combined
approach that detects IR spectral markers of aggregation
using various IR spectroscopy techniques, covering
micro-to-nanoscale ranges, to study the effect of RNA on the
supramolecular architecture of α-synuclein amyloid
aggregates. We show a clear impact of RNA consistent with
enhanced intermolecular forces, likely via a stronger
hydrogen-bonded network stabilizing the cross-β
architecture. AFM-assisted IR spectroscopy was crucial to
assess that the more ordered the aggregates are, the
stronger the structural impact of RNA. In addition, an
RNA-induced reduction of the degree of polymorphism within
the aggregate population is obtained.},
keywords = {alpha-Synuclein: chemistry / alpha-Synuclein: metabolism /
RNA: chemistry / RNA: metabolism / Protein Aggregates /
Amyloid: chemistry / Microscopy, Atomic Force /
Spectrophotometry, Infrared / Humans / alpha-Synuclein (NLM
Chemicals) / RNA (NLM Chemicals) / Protein Aggregates (NLM
Chemicals) / Amyloid (NLM Chemicals)},
cin = {AG Milovanovic (Bonn)},
ddc = {570},
cid = {I:(DE-2719)1013043},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40329536},
doi = {10.1016/j.bpj.2025.04.031},
url = {https://pub.dzne.de/record/279351},
}