The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization
| Autor: | Mariann Bienz, Yoshiki Higuchi, Thomas Schwarz-Romond, Naoki Shibata, P.J.G. Butler, Akira Kikuchi, Marc Fiedler |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Polymers Molecular Sequence Data Cell Dishevelled Proteins macromolecular substances Biology Fibril Models Biological Domain (software engineering) Axin Protein Structural Biology medicine Humans Immunoprecipitation Amino Acid Sequence Binding site Molecular Biology Adaptor Proteins Signal Transducing chemistry.chemical_classification Base Sequence Wnt signaling pathway Sequence Analysis DNA Phosphoproteins Protein Structure Tertiary Cell biology Dishevelled Repressor Proteins Wnt Proteins Microscopy Electron medicine.anatomical_structure Microscopy Fluorescence Biochemistry Polymerization chemistry Cytoplasm Crystallization Ultracentrifugation Signal Transduction |
| Zdroj: | Nature Structural & Molecular Biology. 14:484-492 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb1247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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