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RESEARCH PAPER
-catenin/Axin complex suggests a mechanism for the -catenin destruction complex
1 Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA , 2 Biomolecular Structure and Design Program, University of Washington, Seattle, Washington 98195, USA , 3 Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
The "
-catenin destruction complex" is central to canonical Wnt/-catenin signaling. The scaffolding protein Axin and the tumor suppressor adenomatous polyposis coli protein (APC) are critical components of this complex, required for rapid -catenin turnover. We determined the crystal structure of a complex between -catenin and the -catenin-binding domain of Axin (Axin-CBD). The Axin-CBD forms a helix that occupies the groove formed by the third and fourth armadillo repeats of -catenin and thus precludes the simultaneous binding of other -catenin partners in this region. Our biochemical studies demonstrate that, when phosphorylated, the 20-amino acid repeat region of APC competes with Axin for binding to -catenin. We propose that a key function of APC in the -catenin destruction complex is to remove phosphorylated -catenin product from the active site.
[Keywords: Wnt; -catenin; Axin; adenomatous polyposis coli (APC); crystal structure]
Received August 11, 2003; revised version accepted September 19, 2003.
4 Corresponding author. E-MAIL wxu{at}u.washington.edu; FAX (206) 543-1524.
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