The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization
The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization
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DOI：
10.1038/nsmb1247
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发表时间：
2007-06-01
影响因子：
16.8
通讯作者：
Bienz, Mariann
中科院分区：
文献类型：
--
作者：
Schwarz-Romond, Thomas;Fiedler, Marc;Bienz, Mariann
Wnt信号通路在动物发育过程中控制着许多细胞命运，也是一个主要的癌症通路。disheveled （Dvl）通过与细胞质轴蛋白复合物相互作用来转导Wnt信号。Dvl和Axin都含有一个分子性质和结构未知的DIX结构域。在这里，我们证明了Dvl2的DIX结构域介导动态聚合，这对Dvl2的信号活性至关重要。纯化的结构域以浓度依赖的方式逐渐、可逆地聚合，最终形成原纤维。轴蛋白DIX结构域具有一种新的结构褶皱，主要由β链组成，这些β链参与从头到尾的自相互作用，在晶体中形成细丝。因此，DIX结构域似乎介导了瞬态Wnt信号伙伴的动态相互作用平台的形成，该平台具有高局部浓度的结合位点；这代表了一种以前未被表征的机制原理，通过可逆聚合发出信号。
The Wnt signaling pathway controls numerous cell fates in animal development and is also a major cancer pathway. Dishevelled (Dvl) transduces the Wnt signal by interacting with the cytoplasmic Axin complex. Dvl and Axin each contain a DIX domain whose molecular properties and structure are unknown. Here, we demonstrate that the DIX domain of Dvl2 mediates dynamic polymerization, which is essential for the signaling activity of Dvl2. The purified domain polymerizes gradually, reversibly and in a concentration dependent manner, ultimately forming fibrils. The Axin DIX domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal. The DIX domain thus seems to mediate the formation of a dynamic interaction platform with a high local concentration of binding sites for transient Wnt signaling partners; this represents a previously uncharacterized mechanistic principle, signaling by reversible polymerization.