doi:10.3390/molecules27041293engXu, Catherine K.Castellana-Cruz, MartaChen, Serene W.Du, ZhenMeisl, GeorgLevin, AviadMannini, BenedettaItzhaki, LauraKnowles, Tuomas P. J.Dobson, ChristopherCremades, NuniloKumita, Janet R.The Pathological G51D Mutation in Alpha-Synuclein Oligomers Confers Distinct Structural Attributes and Cellular ToxicityART-2022-131233A 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.2022http://zaguan.unizar.es/record/12020310.3390/molecules27041293http://zaguan.unizar.es/record/120203oai:zaguan.unizar.es:120203info:eu-repo/grantAgreement/ES/MCIU-FEDER/PGC2018-096335-B-100info:eu-repo/grantAgreement/ES/MINECO/RYC-2012-12068Molecules 27, 4 (2022), 1293 [14 pp.]byhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccess