TY  - JOUR
AU  - Intze, Antonia
AU  - Temperini, Maria Eleonora
AU  - Rupert, Jakob
AU  - Polito, Raffaella
AU  - Veber, Alexander
AU  - Puskar, Ljiljana
AU  - Schade, Ulrich
AU  - Ortolani, Michele
AU  - Zacco, Elsa
AU  - Tartaglia, Gian Gaetano
AU  - Giliberti, Valeria
TI  - Effect of RNA on the supramolecular architecture of α-synuclein fibrils.
JO  - Biophysical journal
VL  - 124
IS  - 12
SN  - 0006-3495
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DZNE-2025-00728
SP  - 2005 - 2019
PY  - 2025
AB  - 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.
KW  - alpha-Synuclein: chemistry
KW  - alpha-Synuclein: metabolism
KW  - RNA: chemistry
KW  - RNA: metabolism
KW  - Protein Aggregates
KW  - Amyloid: chemistry
KW  - Microscopy, Atomic Force
KW  - Spectrophotometry, Infrared
KW  - Humans
KW  - alpha-Synuclein (NLM Chemicals)
KW  - RNA (NLM Chemicals)
KW  - Protein Aggregates (NLM Chemicals)
KW  - Amyloid (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40329536
DO  - DOI:10.1016/j.bpj.2025.04.031
UR  - https://pub.dzne.de/record/279351
ER  -