7Q4M

Type II beta-amyloid 42 Filaments from Human Brain

7Q4M の概要

• エントリーDOI: 10.2210/pdb7q4m/pdb
• EMDBエントリー: 13809
• 分子名称: Amyloid-beta precursor protein, UNKNOWN ATOM OR ION (2 entities in total)
• 機能のキーワード: amyloid filaments, abeta42, human brain, cryo-em, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 45200.87

構造登録者

Yang, Y.,Arseni, D.,Zhang, W.,Huang, M.,Lovestam, S.K.A.,Schweighauser, M.,Kotecha, A.,Murzin, A.G.,Peak-Chew, S.Y.,Macdonald, J.,Lavenir, I.,Garringer, H.J.,Gelpi, E.,Newell, K.L.,Kovacs, G.G.,Vidal, R.,Ghetti, B.,Falcon, B.,Scheres, S.H.W.,Goedert, M. (登録日: 2021-11-01, 公開日: 2021-11-24, 最終更新日: 2024-07-17)

主引用文献

Yang, Y.,Arseni, D.,Zhang, W.,Huang, M.,Lovestam, S.,Schweighauser, M.,Kotecha, A.,Murzin, A.G.,Peak-Chew, S.Y.,Macdonald, J.,Lavenir, I.,Garringer, H.J.,Gelpi, E.,Newell, K.L.,Kovacs, G.G.,Vidal, R.,Ghetti, B.,Ryskeldi-Falcon, B.,Scheres, S.H.W.,Goedert, M.
Cryo-EM structures of amyloid-beta 42 filaments from human brains.
Science, 375:167-172, 2022

PubMed Abstract: Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 filaments from human brains. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer’s disease, and type II filaments were found in individuals with familial Alzheimer’s disease and other conditions. The structures of Aβ42 filaments from the brain differ from those of filaments assembled in vitro. By contrast, in knock-in mice, Aβ42 deposits were made of type II filaments. Knowledge of Aβ42 filament structures from human brains may lead to the development of inhibitors of assembly and improved imaging agents.

PubMed: 35025654
DOI: 10.1126/science.abm7285

実験手法

ELECTRON MICROSCOPY (2.8 Å)