Aurel Vlaicu University of Arad, Str. Elena Drăgoi 2-4, RO-310330 Arad, Romania.
Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
Biomolecules. 2019 Mar 23;9(3):116. doi: 10.3390/biom9030116.
Tau is a microtubule-associated protein that promotes microtubule assembly and stability. This protein is implicated in several neurodegenerative diseases, including Alzheimer's. To date, the three-dimensional (3D) structure of tau has not been fully solved, experimentally. Even the most recent information is sometimes controversial in regard to how this protein folds, interacts, and behaves. Predicting the tau structure and its profile sheds light on the knowledge about its properties and biological function, such as the binding to microtubules (MT) and, for instance, the effect on ionic conductivity. Our findings on the tau structure suggest a disordered protein, with discrete portions of well-defined secondary structure, mostly at the microtubule binding region. In addition, the first molecular dynamics simulation of full-length tau along with an MT section was performed, unveiling tau structure when associated with MT and interaction sites. Electrostatics and conductivity were also examined to understand how tau affects the ions in the intracellular fluid environment. Our results bring a new insight into tau and tubulin MT proteins, their characteristics, and the structure⁻function relationship.
tau 是一种微管相关蛋白，可促进微管组装和稳定性。该蛋白与包括阿尔茨海默病在内的几种神经退行性疾病有关。迄今为止，tau 的三维（3D）结构尚未完全通过实验解决。即使是关于这种蛋白质如何折叠、相互作用和表现的最新信息，有时也存在争议。预测 tau 的结构及其形态可以揭示有关其性质和生物学功能的知识，例如与微管（MT）的结合，以及对离子电导率的影响。我们对 tau 结构的研究结果表明，tau 是一种无规卷曲的蛋白质，具有离散的部分，具有明确的二级结构，主要位于微管结合区域。此外，还对全长 tau 与 MT 部分进行了首次分子动力学模拟，揭示了与 MT 结合时 tau 的结构和相互作用位点。还检查了静电和电导率，以了解 tau 如何影响细胞内液环境中的离子。我们的结果为 tau 和微管蛋白 MT 蛋白、它们的特性以及结构⁻功能关系提供了新的见解。
