Title
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling
Author
Antonio Luis Egea-Jimenez, Rodrigo Gallardo, Abel Garcia-Pino, Ylva Ivarsson, Anna Maria Wawrzyniak, Rudra Kashyap, Remy Loris, Joost Schymkowitz, Frederic Rousseau, Pascale Zimmermann
Year
2016
Journal
Nature Communications
Abstract
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.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Biochemistry