Proline-directed Pseudo-phosphorylation at AT8 and PHF1 Epitopes Induces a Compaction of the Paperclip Folding of Tau and Generates a Pathological (MC-1) Conformation
Tau, a neuronal microtubule-associated protein that aggregates in Alzheimer disease is a natively unfolded protein. In solution, Tau adopts a “paperclip” conformation, whereby the N- and C-terminal domains approach each other and the repeat domain (Jeganathan, S., von Bergen, M., Brutlach, H., Steinhoff, H. J., and Mandelkow, E. (2006) Biochemistry 45, 2283-2293). In AD, Tau is in a hyperphosphorylated state. The consequences for microtubule binding or aggregation are a matter the the Tau or in The that the or the state. In the the the domain the C-terminal the the C-terminal domain the repeat In the is the and the that the the repeat The and is a in the the a for Tau in the the aggregation microtubule The a for the Tau in the domains the and the consequences for Tau, a neuronal microtubule-associated protein that aggregates in Alzheimer disease is a natively unfolded protein. 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