120203 20240319081016.0 doi 10.3390/molecules27041293 sideral 131233 ART-2022-131233 eng Xu, Catherine K. The Pathological G51D Mutation in Alpha-Synuclein Oligomers Confers Distinct Structural Attributes and Cellular Toxicity 2022 Access copy available to the general public Unrestricted A wide variety of oligomeric structures are formed during the aggregation of proteins associated with neurodegenerative diseases. Such soluble oligomers are believed to be key toxic species in the related disorders; therefore, identification of the structural determinants of toxicity is of upmost importance. Here, we analysed toxic oligomers of α-synuclein and its pathological variants in order to identify structural features that could be related to toxicity and found a novel structural polymorphism within G51D oligomers. These G51D oligomers can adopt a variety of β-sheet-rich structures with differing degrees of α-helical content, and the helical structural content of these oligomers correlates with the level of induced cellular dysfunction in SH-SY5Y cells. This structure–function relationship observed in α-synuclein oligomers thus presents the α-helical structure as another potential structural determinant that may be linked with cellular toxicity in amyloid-related proteins. info:eu-repo/grantAgreement/ES/MCIU-FEDER/PGC2018-096335-B-100 info:eu-repo/grantAgreement/ES/MINECO/RYC-2012-12068 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.6 2022 CHEMISTRY, MULTIDISCIPLINARY 63 / 178 = 0.354 2022 Q2 T2 BIOCHEMISTRY & MOLECULAR BIOLOGY 97 / 285 = 0.34 2022 Q2 T2 0.704 2022 Pharmaceutical Science 2022 Q1 Chemistry (miscellaneous) 2022 Q2 Drug Discovery 2022 Q2 Physical and Theoretical Chemistry 2022 Q2 Organic Chemistry 2022 Q2 Analytical Chemistry 2022 Q2 Medicine (miscellaneous) 2022 Q2 Molecular Medicine 2022 Q3 6.7 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Castellana-Cruz, Marta Chen, Serene W. Du, Zhen Meisl, Georg Levin, Aviad Mannini, Benedetta Itzhaki, Laura Knowles, Tuomas P. J. Dobson, Christopher Cremades, Nunilo Universidad de Zaragoza (orcid)0000-0002-9138-6687 Kumita, Janet R. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 27, 4 (2022), 1293 [14 pp.] Molecules (Basel, Online) Molecules 1420-3049 4303007 http://zaguan.unizar.es/record/120203/files/texto_completo.pdf Versión publicada 2652738 http://zaguan.unizar.es/record/120203/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:120203 articulos driver 2024-03-18-15:42:12 ARTICLE