Structural Fluctuations and Aggregations of Tau Proteins from X-Ray Single Molecule Observations

Abstract

Intrinsically disordered proteins have very important flexible structures. In order to analyze such proteins, we need new methodology for high-accuracy measurements of three- dimensional (3D) intra-molecular motions. The structure of tau proteins in solution resembles that of a random coil. But, tau proteins in Alzheimer paired helical filaments-like fibers have very little secondary structures. Here, we observed the 3D structural motions of tau proteins using Diffracted X-ray Tracking (DXT) as high-speed x-ray single molecule observations. In DXT, we observed Brownian motions of recombinant tau proteins and his-tagged tau proteins, which are adsorbed on the substrate's surface. These adsorbed tau proteins was reacted to many antibodies and was phosphorylated by several kinases. We succeeded in measuring three-dimensional (3D= 2 axes as polar coordinates) micro-second super-high accuracy (pico-meter scale) motion maps of individual single molecule observations at many conditions of the tau proteins. From dynamic DXT data, for example, the tau protein combined with the antibody was confirmed that structure fluctuation had become slightly large compared with that which is not combined. We discuss the aggregation process of tau protein from these dynamic intra-molecular data under many conditions.