Effect of DNA on Filament Formation of Tau Microtubule-Binding Domain : Structural Dependence of DNA

To examine whether or not DNA accelerates the paired helical filament (PHF) formation of tau, the effect of various types of DNAs on filament formations of three-repeated and four-repeated microtubule-binding domains (3RMBD and 4RMBD, respectively) of tau protein was investigated by monitoring the change of thioflavin S fluorescence intensity, that is parallel to the filament formation. Consequently, the followings were clarified: 1) the structurally rigid double-stranded DNA such as poly(dG-dC) or calf thymus DNA has the high potency of promoting the filament formations of 3RMBD and 4RMBD, 2) the filament formation of 3RMBD was more promoted than that of 4RMBD, due to the intermolecular dimer formation of 3RMBD, 3) the DNA-promoted filament formations of these MBDs were temperature-dependent, and the single-stranded DNA such as poly(dA) or poly(dT) reversely protected 4RMBD from the molecular assembly at 20℃. These are the first report on the function of DNA for the PHF formation of tau protein.