Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
J Mol Biol. 2011 Jan 21;405(3):773-86. doi: 10.1016/j.jmb.2010.11.013. Epub 2010 Nov 16.
The Wnt pathway tumor-suppressor protein Axin coordinates the formation of a critical multiprotein destruction complex that serves to downregulate β-catenin protein levels, thereby preventing target gene activation. Given the lack of structural information on some of the major functional parts of Axin, it remains unresolved how the recruitment and positioning of Wnt pathway kinases, such as glycogen synthase kinase 3β, are coordinated to bring about β-catenin phosphorylation. Using various biochemical and biophysical methods, we demonstrate here that the central region of Axin that is implicated in binding glycogen synthase kinase 3β and β-catenin is natively unfolded. Our results support a model in which the unfolded nature of these critical scaffolding regions in Axin facilitates dynamic interactions with a kinase and its substrate, which in turn act upon each other.
Wnt 通路肿瘤抑制蛋白 Axin 协调形成一个关键的多蛋白破坏复合物，该复合物用于下调β-catenin 蛋白水平，从而防止靶基因激活。鉴于 Axin 的一些主要功能部分缺乏结构信息，Wnt 通路激酶（如糖原合酶激酶 3β）的募集和定位如何协调以实现β-catenin 磷酸化仍未解决。在这里，我们使用各种生化和生物物理方法证明，Axin 中与结合糖原合酶激酶 3β和β-catenin 相关的中心区域是天然无规卷曲的。我们的结果支持这样一种模型，即 Axin 中这些关键支架区域的无规卷曲性质有利于与激酶及其底物的动态相互作用，而激酶及其底物又相互作用。
