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Publication : The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization.

First Author  Schwarz-Romond T Year  2007
Journal  Nat Struct Mol Biol Volume  14
Issue  6 Pages  484-92
PubMed ID  17529994 Mgi Jnum  J:245311
Mgi Id  MGI:5917236 Doi  10.1038/nsmb1247
Citation  Schwarz-Romond T, et al. (2007) The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization. Nat Struct Mol Biol 14(6):484-92
abstractText  The Wnt signaling pathway controls numerous cell fates in animal development and is also a major cancer pathway. Dishevelled (Dvl) transduces the Wnt signal by interacting with the cytoplasmic Axin complex. Dvl and Axin each contain a DIX domain whose molecular properties and structure are unknown. Here, we demonstrate that the DIX domain of Dvl2 mediates dynamic polymerization, which is essential for the signaling activity of Dvl2. The purified domain polymerizes gradually, reversibly and in a concentration dependent manner, ultimately forming fibrils. The Axin DIX domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal. The DIX domain thus seems to mediate the formation of a dynamic interaction platform with a high local concentration of binding sites for transient Wnt signaling partners; this represents a previously uncharacterized mechanistic principle, signaling by reversible polymerization.
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