PUBLICATION
Structure and mechanism of the unique C2 domain of Aida
- Authors
- Zheng, L.S., Liu, Y.T., Chen, L., Wang, Y., Rui, Y.N., Huang, H.Z., Lin, S.Y., Wang, J., Wang, Z.X., Lin, S.C., Wu, J.W.
- ID
- ZDB-PUB-140815-9
- Date
- 2014
- Source
- The FEBS journal 281(20): 4622-32 (Journal)
- Registered Authors
- Huang, Huizhe
- Keywords
- Aida, Axin, C2-domain, Jun N-terminal kinase (JNK), MAP kinases (MAPKs), Membrane proteins, Phosphatidylinositol, X-ray crystallography
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Axin Protein/chemistry*
- Axin Protein/metabolism
- Blotting, Western
- Calcium/metabolism*
- Carrier Proteins/chemistry*
- Carrier Proteins/metabolism
- Circular Dichroism
- Crystallization
- Crystallography, X-Ray
- HEK293 Cells
- Humans
- Immunoprecipitation
- MAP Kinase Kinase 4/metabolism
- Mice
- Molecular Sequence Data
- Phosphatidylinositols/metabolism*
- Protein Conformation
- Protein Structure, Tertiary
- Sequence Homology, Amino Acid
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/metabolism
- PubMed
- 25117763 Full text @ FEBS J.
Citation
Zheng, L.S., Liu, Y.T., Chen, L., Wang, Y., Rui, Y.N., Huang, H.Z., Lin, S.Y., Wang, J., Wang, Z.X., Lin, S.C., Wu, J.W. (2014) Structure and mechanism of the unique C2 domain of Aida. The FEBS journal. 281(20):4622-32.
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 Ca(2+) -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.
Database The atomic coordinates and structure factors of the mouse Aida C2 domain (code: 2QZ5) and the zebrafish Aida C2 domain (code: 2QZQ) have been deposited in the Protein Data Bank (http://www.rcsb.org/) STRUCTURED DIGITAL ABSTRACT: AIDA physically interacts with Axin by anti tag coimmunoprecipitation (View interaction).
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping