Project information
Touching the untouchable; biochemistry of full-length Vangl2 protein

Project Identification
8J25FR012
Project Period
1/2025 - 12/2026
Investor / Pogramme / Project type
Ministry of Education, Youth and Sports of the CR
MU Faculty or unit
Central European Institute of Technology
Cooperating Organization
Institut de Génomique Fonctionnelle

The main gap we have identified in the WNT/PCP field is on mechanistic/structural studies related to full-length Vangl2. Vangl2 is a membrane-embedded protein characterized by the presence of four contiguous transmembrane helices and two cytosolic regions, a highly phosphorylated N-terminus, and a multi-domain C-terminus, which serve as a scaffold upon which the core pathway components as well as positive and negative regulators of the WNT/PCP signaling assemble. By applying state-of-the-art structural biology approaches, we first aim to gain structural insights into Vangl2 activation mechanisms by accomplishing the following: Objective 1: To express and purify Vangl2 protein for structural analysis. To achieve these goals, we collectively have extensive experience in embedding structural information in a physiologically meaningful context in order to translate the findings obtained at atomistic or molecular level to unravel the scaffolding function of the membrane protein Vangl2 in WNT/PCP signaling.

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