Interplay between I308 and Y310 residues in the third repeat of microtubule-binding domain is essential for tau filament formation

Investigation of the mechanism of tau polymerization is indispensable for finding inhibitory conditions or identifying compounds preventing the formation of paired helical filament or oligomers. Tau contains a microtubule-binding domain consisting of three or four repeats in its C-terminal half. It has been considered that the key event in tau polymerization is the formation of a beta-sheet structure arising from a short hexapeptide (306)VQIVYK311 in the third repeat of tau. In this paper, we report for the first time that the C-H center dot center dot center dot pi interaction between Ile308 and Tyr310 is the elemental structural scaffold essential for forming a dry steric zipper structure in tau amyloid fibrils. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.