Structure and mechanism of the unique C2 domain of Aida
Structure and mechanism of the unique C2 domain of Aida
复制标题
DOI：
10.1111/febs.12966
复制
发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Li Zheng;Yi-Tong Liu;Lei Chen;Ying Wang;Yanning Rui;Huixian Huang;Shuyong Lin;Jue Wang;
中科院分区：
文献类型：
--
作者：
Li Zheng;Yi-Tong Liu;Lei Chen;Ying Wang;Yanning Rui;Huixian Huang;Shuyong Lin;Jue Wang;
Axin interactor，dorsalization-associated（Aida）被鉴定为利用其C-末端区域与轴形成抑制剂（Axin）相互作用的调节因子。Aida消除了在斑马鱼胚胎发育期间正确背化所需的Axin介导的Jun N末端激酶活化，因此作为前体化因子发挥作用。在这里，我们报告了Aida C-末端片段的结构，其采用传统的C2结构域拓扑结构。我们还证明了Aida可以以Ca 2+非依赖性方式特异性结合磷酸肌醇，并且能够通过一种新的带正电荷的表面（即基本环）与细胞膜结合。碱性环上带正电荷的斑块突变导致Aida-膜结合不稳定或Aida-Axin相互作用破坏，导致Jun N末端激酶抑制受损。总之，我们的研究结果为C2结构域介导的Aida-膜和Aida-Axin协会提供了分子基础。
Axin interactor, dorsalization‐associated (Aida) was identified as a regulatory factor that utilizes its C‐terminal region to interact with axis formation inhibitor (Axin). Aida abrogates the Axin‐mediated Jun N‐terminal kinase activation required for proper dorsalization during zebrafish embryonic development, and thus functions as a proventralization factor. Here, we report the structure of Aida C‐terminal fragments, which adopt a conventional C2 domain topology. We also demonstrate that Aida can specifically bind to phosphoinositides in a Ca2+‐independent manner, and is able to associate with the cell membrane via a novel positively charged surface, namely a basic loop. Mutation of the positively charged patch on the basic loop leads to destabilization of the Aida–membrane association or disruption of the Aida–Axin interaction, resulting in impaired Jun N‐terminal kinase inhibition. Together, our findings provide a molecular basis for C2 domain‐mediated Aida–membrane and Aida–Axin associations.