Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.

摘要: PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability their domains bind other such receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure syntenin tandem in complex with carboxy-terminal fragment Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2). The reveals tripartite interaction formed via second domain syntenin. Biophysical biochemical experiments establish co-operative binding identify residues crucial PIP2-specific recognition. Experiments cells support importance syntenin-PIP2 plasma targeting c-jun phosphorylation. study contributes our understanding biology key players compartmentalization dynamics.