The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization

Area of Science:

• Molecular Biology
• Cell Signaling
• Structural Biology

Background:

• The Wnt signaling pathway regulates cell fates during development and is implicated in cancer.
• Dishevelled (Dvl) and Axin proteins are key components in Wnt signal transduction.
• The molecular properties and structure of the DIX domains in Dvl and Axin were previously unknown.

Purpose of the Study:

• To investigate the molecular properties and structure of the DIX domains of Dvl and Axin.
• To elucidate the role of the DIX domain in Wnt signal transduction.

Main Methods:

• Protein purification and characterization of the Dvl2 DIX domain.
• Crystallography of the Axin DIX domain.
• Analysis of polymerization dynamics and structural fold.

Main Results:

• The Dvl2 DIX domain undergoes dynamic, reversible polymerization into fibrils, essential for its signaling activity.
• The Axin DIX domain exhibits a novel beta-strand-rich structural fold enabling head-to-tail filament formation.
• These DIX domains form dynamic interaction platforms crucial for Wnt signaling.

Conclusions:

• The DIX domain mediates signaling through reversible polymerization, a novel mechanistic principle.
• Understanding DIX domain polymerization offers new insights into Wnt pathway regulation.
• This mechanism is vital for transient Wnt signaling partner interactions.