ArticleProceedings of the National Academy of Sciences of the United States of America2006
Semirational design of Jun-Fos coiled coils with increased affinity: Universal implications for leucine zipper prediction and design.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- InsiliCoil: An Integrated Software Suite for Coiled Coil Design, Prediction, and Therapeutic Engineering.ACS synthetic biology · 2026Article
- Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors.Nature chemical biology · 2025Article
- Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering.Transcription · 2025Review
- Recent Advances in Computational Prediction of Secondary and Supersecondary Structures from Protein Sequences.Methods in molecular biology (Clifton, N.J.) · 2025Review
- The genetic architecture of protein interaction affinity and specificity.Nature communications · 2024Article
- Exponential Combination ofACS chemical biology · 2024Article
- A multiplexed bacterial two-hybrid for rapid characterization of protein-protein interactions and iterative protein design.Nature communications · 2023Article
- Peptide-based LDH5 inhibitors enter cancer cells and impair proliferation.Cellular and molecular life sciences : CMLS · 2022Article
- The effect of helix-inducing constraints and downsizing upon a transcription block survival-derived functional cJun antagonist.Cell reports. Physical science · 2022Article
- Co-assembled Coiled-Coil Peptide Nanotubes with Enhanced Stability and Metal-Dependent Cargo Loading.ACS omega · 2022Article
- Article
- Ciliary Rootlet Coiled-Coil 2 (crocc2) Is Associated with Evolutionary Divergence and Plasticity of Cichlid Jaw Shape.Molecular biology and evolution · 2021Article
- The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology.Cancers · 2021Review
- Combined computational and intracellular peptide library screening: towards a potent and selective Fra1 inhibitor.RSC chemical biology · 2021Article
- Probing Biomolecular Interactions by a Pattern-Forming Peptide-Conjugate Sensor.Bioconjugate chemistry · 2021Article
- Selective antagonism of cJun for cancer therapy.Journal of experimental & clinical cancer research : CR · 2020Review
- Self-assembly of the bZIP transcription factor ΔFosB.Current research in structural biology · 2020Article
- Split-TALE: A TALE-Based Two-Component System for Synthetic Biology Applications in Planta.Plant physiology · 2019Article
- Selection of Protein-Protein Interactions of Desired Affinities with a Bandpass Circuit.Journal of molecular biology · 2019Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Activator protein-1 (AP-1) is a crucial transcription factor implicated in numerous cancers. For this reason, nine homologues of the AP-1 leucine zipper region have been characterized: Fos (c-Fos, FosB, Fra1, and Fra2), Jun (c-Jun, JunB, and JunD), and semirational library-designed winning peptides FosW and JunW. The latter two were designed to specifically target c-Fos or c-Jun. They have been identified by using protein-fragment complementation assays combined with growth competition. This assay removes nonspecific, unstable, and protease susceptible library members from the pool, leaving winners with excellent drug potential. Thermal melts of all 45 possible dimeric interactions have been surveyed, with the FosW-c-Jun complex displaying a melting temperature (T(m)) of 63 degrees C, compared to only 16 degrees C for wild-type c-Fos-c-Jun interaction. This impressive 70,000-fold K(D) decrease is largely due to optimized core packing, alpha-helical propensity, and electrostatics. Contrastingly, due to a poor c-Fos core, c-Fos-JunW dimerizes with lower affinity. However the T(m) far exceeds wild-type c-Fos-c-Jun and averaged JunW and c-Fos, indicating a preference over either homodimer. Finally, and with wider implications, we have compiled a method for predicting interaction of parallel, dimeric coiled coils, using our T(m) data as a training set, and applying it to 59 bZIP proteins previously reported. Our algorithm, unlike others to date, accounts for helix propensity, which is found to be integral in coiled coil stability. Indeed, in applying the algorithm to these 59(2) bZIP interactions, we were able to correctly identify 92% of all strong interactions and 92% of all noninteracting pairs.
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