Egea-Jimenez, AL, Gallardo, R orcid.org/0000-0003-1584-3564, Garcia-Pino, A et al. (7 more authors) (2016) Frizzled 7 and PIP₂ binding by syntenin PDZ₂ domain supports Frizzled 7 trafficking and signalling. Nature Communications, 7 (1). 12101.
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | ©The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Feb 2020 15:53 |
Last Modified: | 13 Feb 2020 15:53 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/ncomms12101 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:156801 |