%0 Journal Article
%A Röder, Christine
%A Kupreichyk, Tatsiana
%A Gremer, Lothar
%A Schäfer, Luisa U.
%A Pothula, Karunakar R.
%A Ravelli, Raimond B. G.
%A Willbold, Dieter
%A Hoyer, Wolfgang
%A Schröder, Gunnar F.
%T Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils
%J Nature structural & molecular biology
%V 27
%N 7
%@ 1545-9985
%C London [u.a.]
%I Nature Publishing Group
%M FZJ-2020-02940
%P 660 - 667
%D 2020
%X Amyloid deposits consisting of fibrillar islet amyloid polypeptide (IAPP) in pancreatic islets are associated with beta-cell loss and have been implicated in type 2 diabetes (T2D). Here, we applied cryo-EM to reconstruct densities of three dominant IAPP fibril polymorphs, formed in vitro from synthetic human IAPP. An atomic model of the main polymorph, built from a density map of 4.2-Å resolution, reveals two S-shaped, intertwined protofilaments. The segment 21-NNFGAIL-27, essential for IAPP amyloidogenicity, forms the protofilament interface together with Tyr37 and the amidated C terminus. The S-fold resembles polymorphs of Alzheimer's disease (AD)-associated amyloid-β (Aβ) fibrils, which might account for the epidemiological link between T2D and AD and reports on IAPP-Aβ cross-seeding in vivo. The results structurally link the early-onset T2D IAPP genetic polymorphism (encoding Ser20Gly) with the AD Arctic mutation (Glu22Gly) of Aβ and support the design of inhibitors and imaging probes for IAPP fibrils.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 32541895
%U <Go to ISI:>//WOS:000543557100001
%R 10.1038/s41594-020-0442-4
%U https://juser.fz-juelich.de/record/878602