The self-assembly ability of the first microtubule-binding repeat from tau and its modulation by phosphorylation.
The self-assembly ability of the first microtubule-binding repeat from tau and its modulation by phosphorylation.
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DOI：
10.1016/j.bbrc.2006.07.099
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发表时间：
2006-09
影响因子：
3.1
通讯作者：
Lian-Xiu Zhou;Z. Zeng;Jin‐Tang Du;Yu-Fen Zhao;Yan‐Mei Li
中科院分区：
文献类型：
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作者：
Lian-Xiu Zhou;Z. Zeng;Jin‐Tang Du;Yu-Fen Zhao;Yan‐Mei Li
异常磷酸化的 tau 蛋白以成对螺旋丝 (PHF) 的形式聚集，是阿尔茨海默病 (AD) 和其他 tau 蛋白病的标志之一。研究PHF的形成机制及其磷酸化调节具有重要意义。在这项工作中，我们重点关注 tau 的第一个微管结合重复序列，其中包含异常磷酸化位点 Ser262。通过浊度和电子显微镜研究了该重复序列及其相应磷酸化形式的组装倾向。此外，还通过圆二色性 (CD) 和 NMR 光谱分析了两种肽的构象。我们的结果表明，它们都能够自组装，并且 Ser262 磷酸化可以加速组装过程。提出了 PHF 形成的可能机制，并且磷酸化对组装的增强作用为其在阿尔茨海默病中的毒性提供了解释。
Aggregation of abnormally phosphorylated tau in the form of tangs of paired helical filaments (PHFs) is one of the hallmarks of Alzheimer’s disease (AD) and other tauopathies. It is of fundamental importance to study the mechanism of PHF formation and its modulation by phosphorylation. In this work, we have focused on the first microtubule-binding repeat of tau encompassing an abnormal phosphorylation site Ser262. The assembly propensities of this repeat and its corresponding phosphorylated form were investigated by turbidity and electron microscopy. Additionally, conformation of the two peptides is also analyzed through circular dichroism (CD) and NMR spectroscopy. Our results reveal that both of them are capable of self-assembly and phosphorylation at Ser262could speed up the process of assembly. A possible mechanism of PHF formation is proposed and enhancing effect of phosphorylation on assembly provides an explanation to its toxicity in Alzheimer’s disease.