8OWD

Lipidic amyloid-beta(1-40) fibril - polymorph L3

8OWD の概要

• エントリーDOI: 10.2210/pdb8owd/pdb
• 関連するPDBエントリー: 8ovk 8ovm 8owe 8owj 8owk
• EMDBエントリー: 17218 17223 17234 17235 17238 17239
• 分子名称: Amyloid-beta A4 protein (1 entity in total)
• 機能のキーワード: amyloid-beta, fibril, lipids, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 21679.26

構造登録者

Frieg, B.,Han, M.,Giller, K.,Dienemann, C.,Riedel, D.,Becker, S.,Andreas, L.B.,Griesinger, C.,Schroeder, G.F. (登録日: 2023-04-27, 公開日: 2024-03-06)

主引用文献

Frieg, B.,Han, M.,Giller, K.,Dienemann, C.,Riedel, D.,Becker, S.,Andreas, L.B.,Griesinger, C.,Schroder, G.F.
Cryo-EM structures of lipidic fibrils of amyloid-beta (1-40).
Nat Commun, 15:1297-1297, 2024

PubMed Abstract: Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils, as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions.

PubMed: 38351005
DOI: 10.1038/s41467-023-43822-x

実験手法

ELECTRON MICROSCOPY (3.28 Å)