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Phosphorylation of tau protein. Tau self-assembles mainly through the microtubule binding domains/repeat R3 in 3R tau proteins and through R3 and R2 in 4R tau proteins (R2 (275VQIINK280) and R3 (306VQIVYK311) have β-structure). N-terminal and C-terminal regions to the repeats are inhibitory. Hyperphosphorylation of tau neutralizes these basic inhibitory domains, enabling tau-tau interaction (phosphorylation sites indicated by violet Ps) (modified by [15]).
