8BFZ

Amyloid-beta 42 filaments extracted from the human brain with Arctic mutation (E22G) of Alzheimer's disease | ABeta42

8BFZ の概要

• エントリーDOI: 10.2210/pdb8bfz/pdb
• EMDBエントリー: 16022
• 分子名称: Amyloid-beta precursor protein (1 entity in total)
• 機能のキーワード: amyloid, filaments, amyloid-beta, arctic mutation, app, e22g, e693g, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8896.05

構造登録者

Yang, Y.,Zhang, W.J.,Murzin, A.G.,Schweighauser, M.,Huang, M.,Lovestam, S.K.A.,Peak-Chew, S.Y.,Macdonald, J.,Lavenir, I.,Ghetti, B.,Graff, C.,Kumar, A.,Nordberg, A.,Goedert, M.,Scheres, S.H.W. (登録日: 2022-10-27, 公開日: 2023-01-18, 最終更新日: 2025-03-05)

主引用文献

Yang, Y.,Zhang, W.,Murzin, A.G.,Schweighauser, M.,Huang, M.,Lovestam, S.,Peak-Chew, S.Y.,Saito, T.,Saido, T.C.,Macdonald, J.,Lavenir, I.,Ghetti, B.,Graff, C.,Kumar, A.,Nordberg, A.,Goedert, M.,Scheres, S.H.W.
Cryo-EM structures of amyloid-beta filaments with the Arctic mutation (E22G) from human and mouse brains.
Acta Neuropathol, 145:325-333, 2023

PubMed Abstract: The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer's disease. Here, we report the high-resolution cryo-EM structures of Aβ filaments from the frontal cortex of a previously described case (AβPParc1) with the Arctic mutation. Most filaments consist of two pairs of non-identical protofilaments that comprise residues V12-V40 (human Arctic fold A) and E11-G37 (human Arctic fold B). They have a substructure (residues F20-G37) in common with the folds of type I and type II Aβ42. When compared to the structures of wild-type Aβ42 filaments, there are subtle conformational changes in the human Arctic folds, because of the lack of a side chain at G22, which may strengthen hydrogen bonding between mutant Aβ molecules and promote filament formation. A minority of Aβ42 filaments of type II was also present, as were tau paired helical filaments. In addition, we report the cryo-EM structures of Aβ filaments with the Arctic mutation from mouse knock-in line App. Most filaments are made of two identical mutant protofilaments that extend from D1 to G37 (App murine Arctic fold). In a minority of filaments, two dimeric folds pack against each other in an anti-parallel fashion. The App murine Arctic fold differs from the human Arctic folds, but shares some substructure.

PubMed: 36611124
DOI: 10.1007/s00401-022-02533-1

実験手法

ELECTRON MICROSCOPY (2.8 Å)