7Q4B

Type I beta-amyloid 42 Filaments from Human Brain

Summary for 7Q4B

• Entry DOI: 10.2210/pdb7q4b/pdb
• EMDB information: 13800
• Descriptor: Amyloid-beta precursor protein, UNKNOWN ATOM OR ION (3 entities in total)
• Functional Keywords: amyloid filaments, abeta42, human brain, cryo-em, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 10
• Total formula weight: 45200.87

Authors

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. (deposition date: 2021-10-30, release date: 2021-11-24, Last modification date: 2024-07-17)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.5 Å)