8OWK

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

Summary for 8OWK

• Entry DOI: 10.2210/pdb8owk/pdb
• Related: 8ovk 8ovm 8owd 8owe 8owj
• EMDB information: 17218 17223 17234 17235 17238 17239
• Descriptor: Amyloid-beta A4 protein (1 entity in total)
• Functional Keywords: amyloid-beta, fibril, lipids, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 10
• Total formula weight: 43358.52

Authors

Frieg, B.,Han, M.,Giller, K.,Dienemann, C.,Riedel, D.,Becker, S.,Andreas, L.B.,Griesinger, C.,Schroeder, G.F. (deposition date: 2023-04-28, release date: 2024-03-06)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.86 Å)