Study of control in nano-structures of Tau and microtubule under ionic regulation

Abstract

Tau protein found in neurofibrillary tangle inside of a neuron, which is one of two conventional hallmarks of Alzheimer’s disease has been receiving large attention recently. Normal Tau is primarily known to bind to microtubules, an anionic cytoskeleton by electrostatic interaction. It is difficult to observe the conformation of Tau because it has almost no secondary or tertiary structure, so-called an intrinsically disordered protein (IDP) like a random coil. In addition, it is hard to predict the conformation of Tau, a polyampholyte that has both positive and negative charges. Therefore, the molecular structure and mechanism of Tau binding to microtubules are not yet elucidated. The main goal is to build a model of the association between Tau and microtubules and analyze the mechanism by monitoring structural changes of microtubules in the presence of Tau under ionic regulation. The hypothesis is that electrostatic interaction leads to the structural changes of Tau and microtubules. The Tau-microtubule bundles under controlled ionic strength and osmotic pressure were monitored and analyzed by small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), and western blot immunoassay techniques. Here, we suggest that the intermolecular structures of Tau bound to microtubules and changes in the physical property of Tau proteins under ionic regulation.