6HRF

Straight filament from sporadic Alzheimer's disease brain

6HRF の概要

• エントリーDOI: 10.2210/pdb6hrf/pdb
• 関連するPDBエントリー: 5O3T 6HRE
• EMDBエントリー: 0259 0260 3743
• 分子名称: Microtubule-associated protein tau (1 entity in total)
• 機能のキーワード: tau, helical, filament, fibril, amyloid, alzheimer's disease, sf, straight filament, nft, neurofibrillary tangly, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 275519.23

構造登録者

Falcon, B.,Zhang, W.,Schweighauser, M.,Murzin, A.G.,Vidal, R.,Garringer, H.J.,Ghetti, B.,Scheres, S.H.W.,Goedert, M. (登録日: 2018-09-26, 公開日: 2018-10-10, 最終更新日: 2024-07-10)

主引用文献

Falcon, B.,Zhang, W.,Schweighauser, M.,Murzin, A.G.,Vidal, R.,Garringer, H.J.,Ghetti, B.,Scheres, S.H.W.,Goedert, M.
Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold.
Acta Neuropathol., 136:699-708, 2018

PubMed Abstract: The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies.

PubMed: 30276465
DOI: 10.1007/s00401-018-1914-z

実験手法

ELECTRON MICROSCOPY (3.3 Å)