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Cryo-EM structures of tau filaments.
Current Opinion in Structural Biology ( IF 6.8 ) Pub Date : 2020-06-27 , DOI: 10.1016/j.sbi.2020.05.011
Sjors Hw Scheres 1 , Wenjuan Zhang 1 , Benjamin Falcon 1 , Michel Goedert 1
Affiliation  

Assembly of microtubule-associated protein tau into filamentous inclusions underlies many human neurodegenerative diseases, called tauopathies. Tau inclusions display distinct cellular and neuroanatomical distributions in different tauopathies. Morphological and biochemical differences suggest that tau filaments adopt disease-specific molecular conformers, similar to prion strains. Breakthroughs in electron cryo-microscopy have recently yielded atomic structures of tau filaments extracted from the brains of individuals with various tauopathies. Each disease is characterised by a unique tau filament fold, which is conserved among individuals with the same disease. In vitro aggregation yields different structures from those observed in brain. Tau isoform composition, post-translational modifications or interactions with cofactors may determine which structures are formed in brain. Understanding filament formation will be central to deciphering the molecular mechanisms that underlie human tauopathies.

中文翻译:

tau 丝的冷冻电镜结构。

微管相关蛋白 tau 组装成丝状内含物是许多人类神经退行性疾病的基础,称为 taupathies。Tau 包裹体在不同的 tauopathies 中显示出不同的细胞和神经解剖学分布。形态和生化差异表明 tau 丝采用疾病特异性分子构象异构体,类似于朊病毒菌株。电子冷冻显微镜的突破最近产生了从患有各种 tauopath 的个体的大脑中提取的 tau 丝的原子结构。每种疾病的特点是独特的 tau 丝状折叠,它在患有相同疾病的个体中是保守的。体外聚集产生与在大脑中观察到的结构不同的结构。Tau 异构体组成,翻译后修饰或与辅因子的相互作用可能决定大脑中形成哪些结构。了解细丝形成将是破译人类 tauopathies 基础的分子机制的核心。
更新日期:2020-06-27
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