6Y1A

Amyloid fibril structure of islet amyloid polypeptide

6Y1A の概要

• エントリーDOI: 10.2210/pdb6y1a/pdb
• EMDBエントリー: 10669
• 分子名称: Islet amyloid polypeptide, AMINO GROUP (2 entities in total)
• 機能のキーワード: amylin, iapp, amyloid fibril, diabetes, hormone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 62805.23

構造登録者

Roeder, C.,Kupreichyk, T.,Gremer, L.,Schaefer, L.U.,Pothula, K.R.,Ravelli, R.B.G.,Willbold, D.,Hoyer, W.,Schroder, G.F. (登録日: 2020-02-11, 公開日: 2020-03-04, 最終更新日: 2020-07-22)

主引用文献

Roder, C.,Kupreichyk, T.,Gremer, L.,Schafer, L.U.,Pothula, K.R.,Ravelli, R.B.G.,Willbold, D.,Hoyer, W.,Schroder, G.F.
Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-beta fibrils.
Nat.Struct.Mol.Biol., 27:660-667, 2020

PubMed Abstract: 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.

PubMed: 32541895
DOI: 10.1038/s41594-020-0442-4

実験手法

ELECTRON MICROSCOPY (4.2 Å)