Structural evaluation of conformational transition state responsible for self-assembly of tau microtubule-binding domain.
Structural evaluation of conformational transition state responsible for self-assembly of tau microtubule-binding domain.
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DOI：
10.1016/j.bbrc.2004.12.129
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发表时间：
2005-02
影响因子：
3.1
通讯作者：
K. Minoura;Fumie Mizushima;Mari Tokimasa;Shuko Hiraoka;K. Tomoo;M. Sumida;T. Taniguchi;T. Ishida
中科院分区：
文献类型：
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作者：
K. Minoura;Fumie Mizushima;Mari Tokimasa;Shuko Hiraoka;K. Tomoo;M. Sumida;T. Taniguchi;T. Ishida
在阿尔茨海默病患者的大脑中，tau蛋白异常聚集形成不可溶的成对螺旋细丝(PHF)。由于tau微管结合域的第三重复结构(R3)在PHF的形成和自聚集中起重要作用，在20-40%三氟乙醇(TFE)的水溶液中最显著，因此其可能的构象是根据(I)NH和C-αH质子化学位移与水中无规结构的偏差和(Ii)相邻质子之间依赖TFE的NOE效应连接图的组合来估计的。结果表明，N端VQIVYK部分的延伸结构和LSKVTSKC区域的α螺旋状结构为启动R3结构的自组装丝形成提供了结构支架。据我们所知，这是第一次证明了启动tau phf建造所必需的初始结构部分及其结构特征的研究。
In the brains of Alzheimer’s disease patients, the tau protein abnormally aggregates to form an insoluble paired helical filament (PHF). Since the third repeat structure (R3) of the tau microtubule-binding domain plays an essential role in PHF formation and self-aggregates most significantly in an aqueous solution of 20–40% trifluoroethanol (TFE), its possible conformation was estimated from the combination of (i) the TFE-dependent deviations of NH and CαH proton chemical shifts from those of the random structure in water and (ii) the TFE-dependent NOE effect connectivity diagrams between the neighboring protons. Consequently, it was indicated that the extended structure of the N-terminal VQIVYK moiety and the α-helical-like structure of the LSKVTSKC region provide a structural scaffold for initiating the self-assembled filament formation of the R3 structure. To the best of our knowledge, this is the first study that demonstrated the initial structural moiety and its structural feature necessary for starting the tau PHF formation.