8QN6

Amyloid-beta 40 type 2 filament from the leptomeninges of individual with Alzheimer's disease and cerebral amyloid angiopathy

8QN6 の概要

• エントリーDOI: 10.2210/pdb8qn6/pdb
• EMDBエントリー: 18508
• 分子名称: Amyloid-beta A4 protein (1 entity in total)
• 機能のキーワード: amyloid-beta, amyloid, filaments, quadruplet, abeta40, human brain, cryo-em, alzheimer's disease, cerebral amyloid angiopathy, 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: 8671.70

構造登録者

Yang, Y.,Murzin, A.S.,Peak-Chew, S.Y.,Franco, C.,Newell, K.L.,Ghetti, B.,Goedert, M.,Scheres, S.H.W. (登録日: 2023-09-25, 公開日: 2023-12-13, 最終更新日: 2025-01-22)

主引用文献

Yang, Y.,Murzin, A.G.,Peak-Chew, S.,Franco, C.,Garringer, H.J.,Newell, K.L.,Ghetti, B.,Goedert, M.,Scheres, S.H.W.
Cryo-EM structures of A beta 40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy.
Acta Neuropathol Commun, 11:191-191, 2023

PubMed Abstract: We used electron cryo-microscopy (cryo-EM) to determine the structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy. In agreement with previously reported structures, which were solved to a resolution of 4.4 Å, we found three types of filaments. However, our new structures, solved to a resolution of 2.4 Å, revealed differences in the sequence assignment that redefine the fold of Aβ40 peptides and their interactions. Filaments are made of pairs of protofilaments, the ordered core of which comprises D1-G38. The different filament types comprise one, two or three protofilament pairs. In each pair, residues H14-G37 of both protofilaments adopt an extended conformation and pack against each other in an anti-parallel fashion, held together by hydrophobic interactions and hydrogen bonds between main chains and side chains. Residues D1-H13 fold back on the adjacent parts of their own chains through both polar and non-polar interactions. There are also several additional densities of unknown identity. Sarkosyl extraction and aqueous extraction gave the same structures. By cryo-EM, parenchymal deposits of Aβ42 and blood vessel deposits of Aβ40 have distinct structures, supporting the view that Alzheimer's disease and cerebral amyloid angiopathy are different Aβ proteinopathies.

PubMed: 38049918
DOI: 10.1186/s40478-023-01694-8

実験手法

ELECTRON MICROSCOPY (2.4 Å)