School of Chemical Sciences, National Institute of Science Education & Research-Bhubaneswar, OCC of Homi Bhabha National Institute, Khurda, Odisha, India.
Proteins. 2022 Dec;90(12):2103-2115. doi: 10.1002/prot.26401. Epub 2022 Aug 4.
Knowledge of the interaction of the tau fibrils with the cell membrane is critical for the understanding of the underlying tauopathy pathogenesis. Lipid composition is found to affect the conformational ensemble of the tau fibrils. Using coarse-grained and all-atom molecular dynamics simulations we have shown the effect of the lipid composition in modulating the tau structure and dynamics. Molecular dynamics simulations show that tau proteins interact differentially with the zwitterionic compared to the charged lipid membranes. The negatively charged POPG lipid membranes increase the binding propensity of the tau fibrils. The addition of cholesterol is also found to modify the tau binding to the membrane. The binding of tau fibril leads to the concomitant loss of the β-sheet structures across the tau residues alongside the change in the membrane properties (like area per lipid, bilayer thickness, and order parameter of the lipid tails) over the pure bilayers.
了解 tau 原纤维与细胞膜的相互作用对于理解潜在的 tau 病发病机制至关重要。已发现脂质组成会影响 tau 原纤维的构象整体。通过粗粒化和全原子分子动力学模拟，我们展示了脂质组成在调节 tau 结构和动力学方面的作用。分子动力学模拟表明，与带电荷的脂质膜相比，tau 蛋白与两性离子脂质膜的相互作用存在差异。带负电荷的 POPG 脂质膜增加了 tau 原纤维的结合倾向。还发现胆固醇的添加会改变 tau 与膜的结合。tau 原纤维的结合导致 tau 残基上的β-折叠结构同时丢失，同时纯双层膜上的膜性质（如每个脂质的面积、双层厚度和脂质尾部的序参数）发生变化。
