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Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic \u03b2-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19\u201329 S20G, forms pairs of \u03b2-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15\u201325 WT, forms non-toxic labile \u03b2-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19\u201329 S20G may serve as a model for the toxic spine of hIAPP.<\/jats:p>","DOI":"10.7554\/elife.19273","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T08:00:13Z","timestamp":1483430413000},"source":"Crossref","is-referenced-by-count":97,"title":["Atomic structures of fibrillar segments of hIAPP suggest tightly mated \u03b2-sheets are important for cytotoxicity"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-658X","authenticated-orcid":true,"given":"Pascal","family":"Krotee","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States"},{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States"},{"name":"Molecular 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