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TitleCryo-EM structures of lipidic fibrils of amyloid-β (1-40).
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 1297, Year 2024
Publish dateFeb 13, 2024
AuthorsBenedikt Frieg / Mookyoung Han / Karin Giller / Christian Dienemann / Dietmar Riedel / Stefan Becker / Loren B Andreas / Christian Griesinger / Gunnar F Schröder /
PubMed AbstractAlzheimer'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 ...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.
External linksNat Commun / PubMed:38351005 / PubMed Central
MethodsEM (helical sym.)
Resolution2.88 - 3.86 Å
Structure data

17218

8ovk

EMDB-17218, PDB-8ovk:
Lipidic amyloid-beta(1-40) fibril - polymorph L1
Method: EM (helical sym.) / Resolution: 2.88 Å

17223

8ovm

EMDB-17223, PDB-8ovm:
Lipidic amyloid-beta(1-40) fibril - polymorph L2
Method: EM (helical sym.) / Resolution: 3.24 Å

17234

8owd

EMDB-17234, PDB-8owd:
Lipidic amyloid-beta(1-40) fibril - polymorph L3
Method: EM (helical sym.) / Resolution: 3.28 Å

17235

8owe

EMDB-17235, PDB-8owe:
Lipidic amyloid-beta(1-40) fibril - polymorph L2-L3
Method: EM (helical sym.) / Resolution: 3.75 Å

17238

8owj

EMDB-17238, PDB-8owj:
Lipidic amyloid-beta(1-40) fibril - polymorph L2-L2
Method: EM (helical sym.) / Resolution: 3.75 Å

17239

8owk

EMDB-17239, PDB-8owk:
Lipidic amyloid-beta(1-40) fibril - polymorph L3-L3
Method: EM (helical sym.) / Resolution: 3.86 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / amyloid-beta / fibril / lipids

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