Structure and mechanism of the unique C2 domain of Aida

Li Sha Zheng, Yi Tong Liu, Lei Chen, Ying Wang, Yan Ning Rui, Hui Zhe Huang, Shu Yong Lin, Jue Wang, Zhi Xin Wang, Sheng Cai Lin*, Jia Wei Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4622-4632
Number of pages11
JournalFEBS Journal
Volume281
Issue number20
DOIs
Publication statusPublished - Oct 2014
Externally publishedYes

Keywords

  • Axin interactor
  • Axis formation inhibitor (Axin)
  • C2 domain
  • Dorsalization-associated (Aida)
  • Jun N-terminal kinase (JNK)
  • Membrane proteins

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