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DOI | 10.1038/s41586-018-0411-9 |
Cryo-EM structures of tau filaments from Alzheimer's disease | |
Fitzpatrick, Anthony W. P.1; Falcon, Benjamin1; He, Shaoda1; Murzin, Alexey G.1; Murshudov, Garib1; Garringer, Holly J.2; Crowther, R. Anthony1; Ghetti, Bernardino2; Goedert, Michel1; Scheres, Sjors H. W.1 | |
2017-07-13 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 547期号:7662页码:185-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England; USA |
英文摘要 | 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 angstrom 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-beta/beta-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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000405314500032 |
WOS关键词 | PAIRED HELICAL FILAMENTS ; ATOMIC-RESOLUTION STRUCTURE ; AMYLOID FIBRILS ; NEUROFIBRILLARY TANGLES ; FRONTOTEMPORAL DEMENTIA ; RECOMBINANT-TAU ; BETA STRUCTURE ; FINE-STRUCTURE ; PROTEIN-TAU ; IN-VITRO |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202951 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England; 2.Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA |
推荐引用方式 GB/T 7714 | Fitzpatrick, Anthony W. P.,Falcon, Benjamin,He, Shaoda,et al. Cryo-EM structures of tau filaments from Alzheimer's disease[J]. NATURE,2017,547(7662):185-+. |
APA | Fitzpatrick, Anthony W. P..,Falcon, Benjamin.,He, Shaoda.,Murzin, Alexey G..,Murshudov, Garib.,...&Scheres, Sjors H. W..(2017).Cryo-EM structures of tau filaments from Alzheimer's disease.NATURE,547(7662),185-+. |
MLA | Fitzpatrick, Anthony W. P.,et al."Cryo-EM structures of tau filaments from Alzheimer's disease".NATURE 547.7662(2017):185-+. |
条目包含的文件 | 条目无相关文件。 |
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