279351 20260105130940.0 pmc:PMC12256921 pmc 10.1016/j.bpj.2025.04.031 doi pmid:40329536 pmid 0006-3495 ISSN 1542-0086 ISSN altmetric:176970711 altmetric DZNE-2025-00728 English 570 Intze, Antonia 0 Effect of RNA on the supramolecular architecture of α-synuclein fibrils. Cambridge, Mass. 2025 Cell Press article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1751879503_21133 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de alpha-Synuclein NLM Chemicals RNA 63231-63-0 NLM Chemicals Protein Aggregates NLM Chemicals Amyloid NLM Chemicals alpha-Synuclein: chemistry MeSH alpha-Synuclein: metabolism MeSH RNA: chemistry MeSH RNA: metabolism MeSH Protein Aggregates MeSH Amyloid: chemistry MeSH Microscopy, Atomic Force MeSH Spectrophotometry, Infrared MeSH Humans MeSH Temperini, Maria Eleonora 1 Rupert, Jakob P:(DE-2719)9003548 2 dzne Polito, Raffaella 3 Veber, Alexander 4 Puskar, Ljiljana 5 Schade, Ulrich 6 Ortolani, Michele 7 Zacco, Elsa 8 Tartaglia, Gian Gaetano 9 Giliberti, Valeria 10 10.1016/j.bpj.2025.04.031 Vol. 124, no. 12, p. 2005 - 2019 PERI:(DE-600)1477214-0 12 2005 - 2019 Biophysical journal 124 2025 0006-3495 OpenAccess http://pub.dzne.de/record/279351/files/DZNE-2025-00728.pdf OpenAccess pdfa http://pub.dzne.de/record/279351/files/DZNE-2025-00728.pdf?subformat=pdfa oai:pub.dzne.de:279351 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)9003548 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2025 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-21 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-21 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2024-12-21 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2024-12-21 Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 LIC:(DE-HGF)CCBYNCND4 HGFVOC DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-21 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-21 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-21 OpenAccess StatID:(DE-HGF)0510 StatID DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-21 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-21 I:(DE-2719)1013043 AG Milovanovic (Bonn) Molecular Neuroscience 0 journal VDB UNRESTRICTED I:(DE-2719)1013043 FullTexts