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Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/2465
Title: Axin contains three separable domains that confer intramolecular, homodimeric, and heterodimeric interactions involved in distinct functions
Authors: Luo, Wen
Zou, Haiying
Jin, Lihua
Lin, Shuyong
Li, Qinxi
Ye, Zhiyun
Rui, Hongliang
Lin, Shengcai
Keywords: Axin
Intramolecular interaction
Homodimeric interaction
Heterodimeric interaction
Issue Date: Feb-2005
Citation: Journal of biological chemistry, v. 280, no. 6, Feb. 2005, p. 5054-5060
Abstract: Axin is a major scaffold protein, interacting with diverse molecules involved in a number of signaling pathways. Axin can undergo dimer/oligomerization via its DIX domain. Here we show that whereas deletion of the DIX domain at the C terminus rendered Axin incapable of forming dimer, a larger deletion of the C-terminal region restored the ability of Axin to form dimers. Detailed analyses revealed that Axin actually contains two separate domains (D and I) in addition to the DIX domain for homodimerization. The D, I, and DIX domains alone can form homodimers. Interestingly, D and I domains strongly interact with each other, suggesting that Axin can form an intramolecular structure through D and I interaction in the absence of DIX. We also found that DIX-DIX homodimeric interaction is weak but that point mutations in the DIX domain abolished Axin homodimerization. We propose a model to suggest that Axin forms homodimeric interactions through three domains, D, I, and DIX. More importantly, lack of DIX-DIX interaction caused by point mutations in the DIXdomain or deletion causes Axin to form an intramolecular loop through the D and I domains, disallowing homodimerformation. Ccd1 interacts with Axin D domain yet fails to interact with AxinΔDIX, confirming that D is masked after D-I looping. The Axin mutants that are defective in homodimer formation fail to activate JNK but have no effect on β-catenin signaling. Our findings have thus provided a structural basis of conformational changes in Axin, which may underlie the diversity of Axin functions.
Rights: We would like to give credit to American Society for Biochemistry and Molecular Biology for granting us permission to repost this article
URI: http://hdl.handle.net/1783.1/2465
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