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Soluble hIAPP is intrinsically disordered with N\u2010terminal residues 8\u201317 as \u03b1\u2010helices. To understand the contribution of the N\u2010terminal helix to the aggregation of full\u2010length hIAPP, here the oligomerization dynamics of the hIAPP fragment 8\u201320 (hIAPP8\u201020) are investigated with combined computational and experimental approaches. hIAPP8\u201020 forms cross\u2010\u03b2 nanofibrils in silico from isolated helical monomers via the helical oligomers and \u03b1\u2010helices to \u03b2\u2010sheets transition, as confirmed by transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and reversed\u2010phase high performance liquid chromatography. The computational results also suggest that the critical nucleus of aggregation corresponds to hexamers, consistent with a recent mass\u2010spectroscopy study of hIAPP8\u201020 aggregation. hIAPP8\u201020 oligomers smaller than hexamers are helical and unstable, while the \u03b1\u2010to\u2010\u03b2 transition starts from the hexamers. Converted \u03b2\u2010sheet\u2010rich oligomers first form \u03b2\u2010barrel structures as intermediates before aggregating into cross\u2010\u03b2 nanofibrils. This study uncovers a complete picture of hIAPP8\u201020 peptide oligomerization, aggregation nucleation via conformational conversion, formation of \u03b2\u2010barrel intermediates, and assembly of cross\u2010\u03b2 protofibrils, thereby shedding light on the aggregation of full\u2010length hIAPP, a hallmark of pancreatic beta\u2010cell degeneration.<\/jats:p>","DOI":"10.1002\/smll.201805166","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T19:39:27Z","timestamp":1553542767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Amyloid Self\u2010Assembly of hIAPP8\u201020 via the Accumulation of Helical Oligomers, \u03b1\u2010Helix to \u03b2\u2010Sheet Transition, and Formation of \u03b2\u2010Barrel Intermediates"],"prefix":"10.1002","volume":"15","author":[{"given":"Yunxiang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Physics Ningbo University  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