The self-assembly ability of the first microtubule-binding repeat from tau and its modulation by phosphorylation |
| |
Authors: | Zhou Lian-Xiu Zeng Zhi-Yang Du Jin-Tang Zhao Yu-Fen Li Yan-Mei |
| |
Institution: | Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China. |
| |
Abstract: | 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 Ser262 could 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. |
| |
Keywords: | Alzheimer’s disease Tau Microtubule-binding repeat Assembly Phosphorylation |
本文献已被 ScienceDirect PubMed 等数据库收录! |