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Determining the structure(s) of these species and defining their role(s) in assembly is key to devising new routes to control disease. Here, using a combination of chemical kinetics, NMR spectroscopy and other biophysical methods, we identify and structurally characterize the oligomers required for amyloid assembly of the protein \u0394N6, a truncation variant of human \u03b22-microglobulin (\u03b22m) found in amyloid deposits in the joints of patients with dialysis-related amyloidosis. The results reveal an assembly pathway which is initiated by the formation of head-to-head non-toxic dimers and hexamers en route to amyloid fibrils. Comparison with inhibitory dimers shows that precise subunit organization determines amyloid assembly, while dynamics in the C-terminal strand hint to the initiation of cross-\u03b2 structure formation. The results provide a detailed structural view of early amyloid assembly involving structured species that are not cytotoxic.<\/jats:p>","DOI":"10.7554\/elife.46574","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T08:00:32Z","timestamp":1569398432000},"source":"Crossref","is-referenced-by-count":56,"title":["Structural mapping of oligomeric intermediates in an amyloid assembly pathway"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-540X","authenticated-orcid":true,"given":"Theodoros K","family":"Karamanos","sequence":"first","affiliation":[{"name":"The Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom"},{"name":"School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P","family":"Jackson","sequence":"additional","affiliation":[{"name":"The Astbury Centre for 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