Egea-Jimenez…Zimmermann {Nat Commun 7: 12101}
A. Crystal structure of the ternary complex of syntenin PDZ tandem with the C-terminal peptide (PDZ binding motif) from the Frizzled 7 receptor and PtdIns(4,5)P2 (PIP2). B. The PDZ2 domain of syntenin interacts with Frizzled 7 and PIP2 in a co-operative manner. C. Syntenin residues essential for PIP2 interaction supports the recycling of syntenin-Frizzled 7 complexes to the plasma membrane.
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling
Egea-Jimenez AL, Gallardo R, Garcia-Pino A, Ivarsson Y, Wawrzyniak AM, Kashyap R, Loris R, Schymkowitz J, Rousseau F, Zimmermann P.
Nat Commun 2016 Jul.; 7: 12101.
PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2). The crystal structure reveals a tripartite interaction formed via the second PDZ domain of syntenin. Biophysical and biochemical experiments establish co-operative binding of the tripartite complex and identify residues crucial for membrane PIP2-specific recognition. Experiments with cells support the importance of the syntenin-PIP2 interaction for plasma membrane targeting of Frizzled 7 and c-jun phosphorylation. This study contributes to our understanding of the biology of PDZ proteins as key players in membrane compartmentalization and dynamics.
PubMed: 27386966. Doi: 10.1038/ncomms12101.
