Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
FEBS Lett. 2010 Oct 8;584(19):4233-6. doi: 10.1016/j.febslet.2010.09.012. Epub 2010 Sep 17.
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 (306)VQIVYK(311) 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.
研究 tau 聚合的机制对于寻找抑制条件或鉴定防止形成双链螺旋丝或低聚物的化合物是必不可少的。tau 包含一个微管结合域，其 C 端的一半由三个或四个重复组成。人们认为 tau 聚合的关键事件是由 tau 第三个重复中的短六肽 (306)VQIVYK(311) 形成 β- 片层结构。在本文中，我们首次报道了 Ile308 和 Tyr310 之间的 C-H⋯π 相互作用是 tau 淀粉样纤维中形成干燥“空间拉链”结构的基本结构支架。
