ArticleNature chemical biology2023
Combinatorial protein dimerization enables precise multi-input synthetic computations.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Programmable DNA-Based Dimerization Networks for Dynamic and Competitive Control of Transcription.Journal of the American Chemical Society · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Repurposing nuclear receptors for ligand-responsive liquid condensate formation and gene regulation.Nature communications · 2026Article
- Expanding the toolkit of LacI/GalR chimeras.PloS one · 2026Article
- Synthetic closed-loop gene circuit for phenylalanine regulation.Nucleic acids research · 2025Article
- Dimeric copper peptide incorporated hydrogel for promoting diabetic wound healing.Nature communications · 2025Article
- A generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors.Nature communications · 2025Article
- Concentration-Dependent CsrA Regulation of theACS synthetic biology · 2025Article
- Caspase 9-induced apoptosis enables efficient fetal cell ablation and disease modeling.Nature communications · 2025Article
- Engineering conditional protein-protein interactions for dynamic cellular control.Biotechnology advances · 2024Review
- A Gene-Switch Platform Interfacing with Reactive Oxygen Species Enables Transcription Fine-Tuning by Soluble and Volatile Pharmacologics and Food Additives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Accelerating Genetic Sensor Development, Scale-up, and Deployment Using Synthetic Biology.Biodesign research · 2024Article
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Target-dependent RNA polymerase as universal platform for gene expression control in response to intracellular molecules.Nature communications · 2023Article
- Evolution of molecular switches for regulation of transgene expression by clinically licensed gluconate.Nucleic acids research · 2023Article
- Synthesizing cellular LOGIC.Nature chemical biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial transcription factors (TFs) with helix-turn-helix (HTH) DNA-binding domains have been widely explored to build orthogonal transcriptional regulation systems in mammalian cells. Here we capitalize on the modular structure of these proteins to build a framework for multi-input logic gates relying on serial combinations of inducible protein-protein interactions. We found that for some TFs, their HTH domain alone is sufficient for DNA binding. By fusing the HTH domain to TFs, we established dimerization dependent rather than DNA-binding-dependent activation. This enabled us to convert gene switches from OFF-type into more widely applicable ON-type systems and to create mammalian gene switches responsive to new inducers. By combining both OFF and ON modes of action, we built a compact, high-performance bandpass filter. Furthermore, we were able to show cytosolic and extracellular dimerization. Cascading up to five pairwise fusion proteins yielded robust multi-input AND logic gates. Combinations of different pairwise fusion proteins afforded a variety of 4-input 1-output AND and OR logic gate configurations.
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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.