Novel tau filament fold in corticobasal degeneration

doi:10.1038/s41586-020-2043-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2043-0
	Novel tau filament fold in corticobasal degeneration
	Izumi, Natsuko 1; Shoji, Keisuke 1,2; Suzuki, Yutaka 3; Katsuma, Susumu 4; Tomari, Yukihide 1,3
	2020-01-29
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	580 期号:7802 页码:283-+
文章类型	Article
语种	英语
国家	England; Japan; USA
英文关键词	Cyro-electron microscopy of tau filaments from people with corticobasal degeneration reveals a previously unseen four-layered fold, distinct from the filament structures seen in Alzheimer' s disease, Pick' s disease and chronic traumatic encephalopathy. Corticobasal degeneration (CBD) is a neurodegenerative tauopathy-a class of disorders in which the tau protein forms insoluble inclusions in the brain-that is characterized by motor and cognitive disturbances(1-3). The H1 haplotype of MAPT (the tau gene) is present in cases of CBD at a higher frequency than in controls(4,5), and genome-wide association studies have identified additional risk factors(6). By histology, astrocytic plaques are diagnostic of CBD7,8 by SDS-PAGE, so too are detergent-insoluble, 37 kDa fragments of tau(9). Like progressive supranuclear palsy, globular glial tauopathy and argyrophilic grain disease(10), CBD is characterized by abundant filamentous tau inclusions that are made of isoforms with four microtubule-binding repeats(11-15). This distinguishes such ' 4R' tauopathies from Pick' s disease (the filaments of which are made of three-repeat (3R) tau isoforms) and from Alzheimer' s disease and chronic traumatic encephalopathy (CTE) (in which both 3R and 4R isoforms are found in the filaments)(16). Here we use cryo-electron microscopy to analyse the structures of tau filaments extracted from the brains of three individuals with CBD. These filaments were identical between cases, but distinct from those seen in Alzheimer' s disease, Pick' s disease and CTE17-19. The core of a CBD filament comprises residues lysine 274 to glutamate 380 of tau, spanning the last residue of the R1 repeat, the whole of the R2, R3 and R4 repeats, and 12 amino acids after R4. The core adopts a previously unseen four-layered fold, which encloses a large nonproteinaceous density. This density is surrounded by the side chains of lysine residues 290 and 294 from R2 and lysine 370 from the sequence after R4.
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:000522805200001
WOS关键词	PAIRED HELICAL FILAMENTS ; PROGRESSIVE SUPRANUCLEAR PALSY ; BEAM-INDUCED MOTION ; CORTICONIGRAL DEGENERATION ; ABNORMAL PHOSPHORYLATION ; NEUROFIBRILLARY CHANGES ; NEURONAL ACHROMASIA ; ASTROCYTIC PLAQUES ; BAYESIAN-APPROACH ; PROTEIN
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计	被引频次：324[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281150
专题	地球科学资源环境科学气候变化
作者单位	1.Univ Tokyo, Inst Quantitat Biosci, Lab RNA Funct, Tokyo, Japan; 2.Utsunomiya Univ, Sch Agr, Dept Agrobiol & Bioresources, Utsunomiya, Tochigi, Japan; 3.Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Kashiwa, Chiba, Japan; 4.Univ Tokyo, Grad Sch Agr & Life Sci, Dept Agr & Environm Biol, Tokyo, Japan
推荐引用方式 GB/T 7714	Izumi, Natsuko,Shoji, Keisuke,Suzuki, Yutaka,et al. Novel tau filament fold in corticobasal degeneration[J]. NATURE,2020,580(7802):283-+.
APA	Izumi, Natsuko,Shoji, Keisuke,Suzuki, Yutaka,Katsuma, Susumu,&Tomari, Yukihide.(2020).Novel tau filament fold in corticobasal degeneration.NATURE,580(7802),283-+.
MLA	Izumi, Natsuko,et al."Novel tau filament fold in corticobasal degeneration".NATURE 580.7802(2020):283-+.