Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.
The "beta-catenin destruction complex" is central to canonical Wnt/beta-catenin signaling. The scaffolding protein Axin and the tumor suppressor adenomatous polyposis coli protein (APC) are critical components of this complex, required for rapid beta-catenin turnover. We determined the crystal structure of a complex between beta-catenin and the beta-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 beta-catenin and thus precludes the simultaneous binding of other beta-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 beta-catenin. We propose that a key function of APC in the beta-catenin destruction complex is to remove phosphorylated beta-catenin product from the active site.
Xing
Yi
Y
Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA.
Clements
Wilson K
WK
Kimelman
David
D
Xu
Wenqing
W
D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D060466:Axin Protein; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000378:metabolism; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin