ArticleProtein science : a publication of the Protein Society2014
Increasing the affinity of selective bZIP-binding peptides through surface residue redesign.
Article in Protein science : a publication of the Protein Society, 2014. 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, 26 citations in OpenAlex.
- InsiliCoil: An Integrated Software Suite for Coiled Coil Design, Prediction, and Therapeutic Engineering.ACS synthetic biology · 2026Article
- The genetic architecture of protein interaction affinity and specificity.Nature communications · 2024Article
- The art of designed coiled-coils for the regulation of mammalian cells.Cell chemical biology · 2024Review
- Article
- Prerequisites for Stabilizing Long-Range Synergistic Interactions amongBiochemistry · 2022Article
- Coiled-coil heterodimers with increased stability for cellular regulation and sensing SARS-CoV-2 spike protein-mediated cell fusion.Scientific reports · 2021Article
- Selective antagonism of cJun for cancer therapy.Journal of experimental & clinical cancer research : CR · 2020Review
- Coiled-Coils: the Molecular Zippers that Self-Assemble Protein Nanostructures.International journal of molecular sciences · 2020Review
- Selection of Protein-Protein Interactions of Desired Affinities with a Bandpass Circuit.Journal of molecular biology · 2019Article
- Functional mapping of brain synapses by the enriching activity-marker SynaptoZip.Nature communications · 2017Article
- Construction of a Chassis for a Tripartite Protein-Based Molecular Motor.ACS synthetic biology · 2017Article
- Designing helical peptide inhibitors of protein-protein interactions.Current opinion in structural biology · 2016Review
- De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity.Science (New York, N.Y.) · 2016Article
- Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties.Scientific reports · 2015Article
- Protein engineering in the 21st century.Protein science : a publication of the Protein Society · 2015Article
- Data-driven prediction and design of bZIP coiled-coil interactions.PLoS computational biology · 2015Article
- A set of computationally designed orthogonal antiparallel homodimers that expands the synthetic coiled-coil toolkit.Journal of the American Chemical Society · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The coiled-coil dimer is a prevalent protein interaction motif that is important for many cellular processes. The basic leucine-zipper (bZIP) transcription factors are one family of proteins for which coiled-coil mediated dimerization is essential for function, and misregulation of bZIPs can lead to disease states including cancer. This makes coiled coils attractive protein-protein interaction targets to disrupt using engineered molecules. Previous work designing peptides to compete with native coiled-coil interactions focused primarily on designing the core residues of the interface to achieve affinity and specificity. However, folding studies on the model bZIP GCN4 show that coiled-coil surface residues also contribute to binding affinity. Here we extend a prior study in which peptides were designed to bind tightly and specifically to representative members of each of 20 human bZIP families. These "anti-bZIP" peptides were designed with an emphasis on target-binding specificity, with contributions to design-target specificity and affinity engineered considering only the coiled-coil core residues. High-throughput testing using peptide arrays indicated many successes. We have now measured the binding affinities and specificities of anti-bZIPs that bind to FOS, XBP1, ATF6, and CREBZF in solution and tested whether redesigning the surface residues can increase design-target affinity. Incorporating residues that favor helix formation into the designs increased binding affinities in all cases, providing low-nanomolar binders of each target. However, changes in surface electrostatic interactions sometimes changed the binding specificity of the designed peptides.
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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.