Liu YT, Dan QJ, Wang J, Feng Y, Chen L, Liang J, Li Q, Lin SC, Wang ZX, Wu JW*. Molecular basis of Wnt activation via the DIX-domain protein Ccd1. JOURNAL OF BIOLOGICAL CHEMISTRY 286(10):8597-608, 2011

Abstract The Wnt signaling plays pivotal roles in embryogenesis and cancer, and the three DIX domain-containing proteins, Dvl, Axin, and Ccd1, play distinct roles in the initiation and regulation of canonical Wnt signaling. Overexpressed Dvl has a tendency to form large polymers in a cytoplasmic punctate pattern, whereas the biologically active Dvl in fact forms low molecular weight oligomers. The molecular basis for how the polymeric sizes of Dvl proteins are controlled upon Wnt signaling remains unclear. Here we show that Ccd1 up-regulates canonical Wnt signaling via acting synergistically with Dvl. We determined the crystal structures of wild type Ccd1-DIX and mutant Dvl1-DIX(Y17D), which pack into ""head-to-tail"" helical filaments. Structural analyses reveal two sites crucial for int......