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Rational design of inhibitors of IAPP amyloid formation has therapeutic potential, but is hampered by the lack of structural information on inhibitor complexes of the conformationally flexible, aggregation-prone IAPP. Here we characterize a \u03b2-hairpin conformation of IAPP in complex with the engineered binding protein \u03b2-wrapin HI18. The \u03b2-strands correspond to two amyloidogenic motifs, 12-LANFLVH-18 and 22-NFGAILS-28, which are connected by a turn established around Ser-20. Besides backbone hydrogen bonding, the IAPP:HI18 interaction surface is dominated by non-polar contacts involving hydrophobic side chains of the IAPP \u03b2-strands. Apart from monomers, HI18 binds oligomers and fibrils and inhibits IAPP aggregation and toxicity at low substoichiometric concentrations. The IAPP \u03b2-hairpin can serve as a molecular recognition motif enabling control of IAPP aggregation.<\/jats:p>","DOI":"10.1038\/srep33474","type":"journal-article","created":{"date-parts":[[2016,9,19]],"date-time":"2016-09-19T10:09:21Z","timestamp":1474279761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["\u03b2-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor"],"prefix":"10.1038","volume":"6","author":[{"given":"Ewa A.","family":"Mirecka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Feuerstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Gremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar F.","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Stoldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Willbold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hoyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,19]]},"reference":[{"key":"BFsrep33474_CR1","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nrm3810","volume":"15","author":"TP Knowles","year":"2014","unstructured":"Knowles, T. 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