ArticleNature communications2019
Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Discovery of SHANK1-PDZ Peptide-Fragment Inhibitors Using a Dynamic Ligation Screening Strategy.Biochemistry · 2026Article
- Synaptic signatures and disease vulnerabilities of layer 5 pyramidal neurons.Nature communications · 2025Article
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- Engineering memory with an extrinsically disordered kinase.Science advances · 2023Article
- Yeast Display Enables Identification of Covalent Single-Domain Antibodies against Botulinum Neurotoxin Light Chain A.ACS chemical biology · 2022Article
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- High-Resolution Fluorescence Imaging Combined With Computer Simulations to Quantitate Surface Dynamics and Nanoscale Organization of Neuroligin-1 at Synapses.Frontiers in synaptic neuroscience · 2022Article
- Bioorthogonal labeling of transmembrane proteins with non-canonical amino acids unveils masked epitopes in live neurons.Nature communications · 2021Article
- Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons.Cell reports · 2021Article
- Identification of β-strand mediated protein-protein interaction inhibitors using ligand-directed fragment ligation.Chemical science · 2021Article
- Small-molecule inhibitors of the PDZ domain of Dishevelled proteins interrupt Wnt signalling.Magnetic resonance (Gottingen, Germany) · 2021Article
- Using yeast two-hybrid system and molecular dynamics simulation to detect venom protein-protein interactions.Current research in toxicology · 2021Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Designing highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces. We report here a strategy that uses a semi-rational approach to separate the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by using phage display selection coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to contact the target interface. We apply this approach to specifically bind a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides a paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules.
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