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The core of these fibrils features a serpentine arrangement with seven or eight \u03b2 strands, secured by a hydrophobic cavity and a salt bridge between arginine-85 and aspartic acid\u2013101 in the G85R fibril. We demonstrate that these mutant fibrils are notably more toxic and capable of promoting the aggregation of wild-type SOD1 more effectively, causing mitochondrial impairment and activating ferroptosis in cell cultures, compared to wild-type SOD1 fibrils. Our study provides insights into the structural mechanisms by which SOD1 mutants aggregate and induce cytotoxicity in ALS.<\/jats:p>","DOI":"10.1126\/sciadv.ado8499","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:58:32Z","timestamp":1730296712000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":29,"title":["Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5377-3168","authenticated-orcid":true,"given":"Li-Qiang","family":"Wang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430072, 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