ArticlePloS one2013
Prevalence, specificity and determinants of lipid-interacting PDZ domains from an in-cell screen and in vitro binding experiments.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- The planar cell polarity protein Vangl2 interacts with the PDZ-domains of Scribble but not with a unique PDZ-like domain in Inturned.FEBS letters · 2026Article
- PDZ scaffolds regulate extracellular vesicle production, composition, and uptake.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Human PDZome 2.0: Characterization of a New Resource to Test for PDZ Interactions by Yeast Two-Hybrid.Membranes · 2023Article
- Biological Role and Aberrant Overexpression of Syntenin-1 in Cancer: Potential Role as a Biomarker and Therapeutic Target.Biomedicines · 2023Review
- Integrated analysis of Shank1 PDZ interactions with C-terminal and internal binding motifs.Current research in structural biology · 2021Article
- PDZ Sample Quality Assessment by Biochemical and Biophysical Characterizations.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways.Experimental neurology · 2020Article
- Specificity in PDZ-peptide interaction networks: Computational analysis and review.Journal of structural biology: X · 2020Review
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Polyphosphoinositide-Binding Domains: Insights from Peripheral Membrane and Lipid-Transfer Proteins.Advances in experimental medicine and biology · 2019Review
- Three-Dimensional Cellular Raman Analysis: Evidence of Highly Ordered Lipids Within Cell Nuclei.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- Structure function relations in PDZ-domain-containing proteins: Implications for protein networks in cellular signalling.Journal of biosciences · 2018Review
- Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.Nature communications · 2016Article
- Membrane Binding and Modulation of the PDZ Domain of PICK1.Membranes · 2015Review
- Biochemical Large-Scale Interaction Analysis of Murine Olfactory Receptors and Associated Signaling Proteins with Post-Synaptic Density 95, Drosophila Discs Large, Zona-Occludens 1 (PDZ) Domains.Molecular & cellular proteomics : MCP · 2015Article
- Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The human PDZome: a gateway to PSD95-Disc large-zonula occludens (PDZ)-mediated functions.Molecular & cellular proteomics : MCP · 2013Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPDZ domains are highly abundant protein-protein interaction modules involved in the wiring of protein networks. Emerging evidence indicates that some PDZ domains also interact with phosphoinositides (PtdInsPs), important regulators of cell polarization and signaling. Yet our knowledge on the prevalence, specificity, affinity, and molecular determinants of PDZ-PtdInsPs interactions and on their impact on PDZ-protein interactions is very limited. METHODOLOGY/PRINCIPAL
findingsWe screened the human proteome for PtdInsPs interacting PDZ domains by a combination of in vivo cell-localization studies and in vitro dot blot and Surface Plasmon Resonance (SPR) experiments using synthetic lipids and recombinant proteins. We found that PtdInsPs interactions contribute to the cellular distribution of some PDZ domains, intriguingly also in nuclear organelles, and that a significant subgroup of PDZ domains interacts with PtdInsPs with affinities in the low-to-mid micromolar range. In vitro specificity for the head group is low, but with a trend of higher affinities for more phosphorylated PtdInsPs species. Other membrane lipids can assist PtdInsPs-interactions. PtdInsPs-interacting PDZ domains have generally high pI values and contain characteristic clusters of basic residues, hallmarks that may be used to predict additional PtdInsPs interacting PDZ domains. In tripartite binding experiments we established that peptide binding can either compete or cooperate with PtdInsPs binding depending on the combination of ligands. CONCLUSIONS/SIGNIFICANCE: Our screen substantially expands the set of PtdInsPs interacting PDZ domains, and shows that a full understanding of the biology of PDZ proteins will require a comprehensive insight into the intricate relationships between PDZ domains and their peptide and lipid ligands.
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