ArticleProceedings of the National Academy of Sciences of the United States of America2014
Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Genome-wide meta-analysis associates GPSM1 with type 2 diabetes, a plausible gene involved in skeletal muscle function.Journal of human genetics · 2020Pooled it
- No Time to Fold: Intrinsically Disordered Microproteins in Action.Biochemistry · 2026Review
- Sequence Engineering at Non-motif Modulator Residues Yields a Peptide That Effectively Targets a Single PDZ Protein in a Disease-relevant Cellular Context.Journal of molecular biology · 2026Article
- Accurate affinity models for SH2 domains from peptide binding assays and free-energy regression.Protein science : a publication of the Protein Society · 2025Article
- Sequence engineering at non-motif modulator residues yields a peptide that effectively targets a single PDZ protein in a disease-relevant cellular context.bioRxiv : the preprint server for biology · 2025Article
- Inhibitors of Tax1-PDZ Interactions Block HTLV-1 Viral Transmission by Changing EV Composition.Journal of extracellular vesicles · 2025Article
- Emerging functions of Plakophilin 4 in the control of cell contact dynamics.Cell communication and signaling : CCS · 2025Review
- PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.Protein science : a publication of the Protein Society · 2025Article
- Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Selection of Nucleotide-Encoded Mass Libraries of Macrocyclic Peptides for Inaccessible Drug Targets.Chemical reviews · 2024Review
- A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.bioRxiv : the preprint server for biology · 2024Article
- The Scribble-SGEF-Dlg1 complex regulates E-cadherin and ZO-1 stability, turnover and transcription in epithelial cells.Journal of cell science · 2024Article
- FaSTPACE: a fast and scalable tool for peptide alignment and consensus extraction.NAR genomics and bioinformatics · 2024Article
- The non-catalytic domains of O-GlcNAc cycling enzymes present new opportunities for function-specific control.Current opinion in chemical biology · 2024Review
- PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.bioRxiv : the preprint server for biology · 2024Article
- The Scribble/SGEF/Dlg1 complex regulates the stability of apical junctions in epithelial cells.bioRxiv : the preprint server for biology · 2024Article
- Discovery and Characterization of Linear Motif Mediated Protein-Protein Complexes.Advances in experimental medicine and biology · 2024Article
- Autoregulation of the LIM kinases by their PDZ domain.Nature communications · 2023Article
- Scribble, Lgl1, and myosin IIA interact with α-/β-catenin to maintain epithelial junction integrity.Cell adhesion & migration · 2023Article
- Discovery and pharmacophoric characterization of chemokine network inhibitors using phage-display, saturation mutagenesis and computational modelling.Nature communications · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between full-length Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit α-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein-protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.