Interplay between I308 and Y310 residues in the third repeat of microtubule-binding domain is essential for tau filament formation |
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Authors: | Keiko Naruto Ryouhei Okuda Yasuko In Koji Tomoo |
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Affiliation: | a Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-11, Japan b Behavioral and Medical Sciences Research Consortium, 2-5-7 Tamachi, Akashi, Hyogo 673-0025, Japan |
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Abstract: | 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 β-sheet structure arising from a short hexapeptide 306VQIVYK311 in the third repeat of tau. In this paper, we report for the first time that the C-H?π interaction between Ile308 and Tyr310 is the elemental structural scaffold essential for forming a dry “steric zipper” structure in tau amyloid fibrils. |
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Keywords: | Tau Microtubule-binding domain Tyrosine residue Isoleucine residue Filament formation C-H?π interaction |
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