TY  - JOUR
AU  - Röder, Christine
AU  - Kupreichyk, Tatsiana
AU  - Gremer, Lothar
AU  - Schäfer, Luisa U.
AU  - Pothula, Karunakar R.
AU  - Ravelli, Raimond B. G.
AU  - Willbold, Dieter
AU  - Hoyer, Wolfgang
AU  - Schröder, Gunnar F.
TI  - Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils
JO  - Nature structural & molecular biology
VL  - 27
IS  - 7
SN  - 1545-9985
CY  - London [u.a.]
PB  - Nature Publishing Group
M1  - FZJ-2020-02940
SP  - 660 - 667
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 32541895
UR  - <Go to ISI:>//WOS:000543557100001
DO  - DOI:10.1038/s41594-020-0442-4
UR  - https://juser.fz-juelich.de/record/878602
ER  -