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The p3 peptides have been mis-named \u2018non-amyloidogenic\u2019. Here we show p3<jats:sub>40\/42<\/jats:sub> peptides rapidly form amyloid fibrils, with kinetics dominated by secondary nucleation. Importantly, cross-seeding experiments, with full-length A\u03b2 induces a strong nucleation between p3 and A\u03b2 peptides. The cross-seeding interaction is highly specific, and occurs only when the C-terminal residues are matched. We have imaged membrane interactions with p3, and monitored Ca<jats:sup>2+<\/jats:sup> influx and cell viability with p3 peptide. Together this data suggests the N-terminal residues influence, but are not essential for, membrane disruption. Single particle analysis of TEM images indicates p3 peptides can form ring-like annular oligomers. Patch-clamp electrophysiology, shows p3<jats:sub>42<\/jats:sub> oligomers are capable of forming large ion-channels across cellular membranes. A role for p3 peptides in disease pathology should be considered as p3 peptides are cytotoxic and cross-seed A\u03b2 fibril formation in vitro.<\/jats:p>","DOI":"10.1038\/s41467-025-57341-4","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T19:05:16Z","timestamp":1740683116000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The p3 peptides (A\u03b217-40\/42) rapidly form amyloid fibrils that cross-seed with full-length A\u03b2"],"prefix":"10.1038","volume":"16","author":[{"given":"Yao","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea P.","family":"Torres-Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anum","family":"Khursheed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogachan","family":"Tahirbegi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-6043","authenticated-orcid":false,"given":"Patrick N.","family":"Pallier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-2964","authenticated-orcid":false,"given":"John H.","family":"Viles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"57341_CR1","unstructured":"Prince, M. et al. 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