5O3O

Pronase-treated paired helical filament in Alzheimer's disease brain

5O3O の概要

• エントリーDOI: 10.2210/pdb5o3o/pdb
• EMDBエントリー: 3742
• 分子名称: Microtubule-associated protein tau (1 entity in total)
• 機能のキーワード: tau, amyloid, cross-beta, beta-helix, protein fibril
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytosol : P10636
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 79401.41

構造登録者

Fitzpatrick, A.W.P.,Falcon, B.,He, S.,Murzin, A.G.,Murshudov, G.,Garringer, H.G.,Crowther, R.A.,Ghetti, B.,Goedert, M.,Scheres, S.H.W. (登録日: 2017-05-24, 公開日: 2017-07-26, 最終更新日: 2024-05-15)

主引用文献

Fitzpatrick, A.W.P.,Falcon, B.,He, S.,Murzin, A.G.,Murshudov, G.,Garringer, H.J.,Crowther, R.A.,Ghetti, B.,Goedert, M.,Scheres, S.H.W.
Cryo-EM structures of tau filaments from Alzheimer's disease.
Nature, 547:185-190, 2017

PubMed Abstract: Alzheimer's disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4-3.5 Å resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer's disease. Filament cores are made of two identical protofilaments comprising residues 306-378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases.

PubMed: 28678775
DOI: 10.1038/nature23002

実験手法

ELECTRON MICROSCOPY (3.5 Å)