ArticleProceedings of the National Academy of Sciences of the United States of America2012
Engineering robust control of two-component system phosphotransfer using modular scaffolds.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Engineering synthetic phosphorylation signaling networks in human cells.bioRxiv : the preprint server for biology · 2023Article
- Engineering transmembrane signal transduction in synthetic membranes using two-component systems.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Bacterial two-component systems as sensors for synthetic biology applications.Current opinion in systems biology · 2021Article
- An engineered protein-phosphorylation toggle network with implications for endogenous network discovery.Science (New York, N.Y.) · 2021Article
- Programmable protein circuit design.Cell · 2021Review
- An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells.Nature communications · 2020Article
- Designed Asymmetric Protein Assembly on a Symmetric Scaffold.Angewandte Chemie (International ed. in English) · 2020Article
- Conjugated Protein Domains as Engineered Scaffold Proteins.Bioconjugate chemistry · 2020Review
- The Relationship between Effective Molarity and Affinity Governs Rate Enhancements in Tethered Kinase-Substrate Reactions.Biochemistry · 2020Article
- Ancient origins of allosteric activation in a Ser-Thr kinase.Science (New York, N.Y.) · 2020Article
- Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy.Nucleic acids research · 2019Article
- Rewiring bacterial two-component systems by modular DNA-binding domain swapping.Nature chemical biology · 2019Article
- Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.Nucleic acids research · 2019Article
- Article
- Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth.PLoS pathogens · 2017Article
- An operational view of intercellular signaling pathways.Current opinion in systems biology · 2017Article
- Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes.Molecular biology and evolution · 2016Article
- Core signalling motif displaying multistability through multi-state enzymes.Journal of the Royal Society, Interface · 2016Article
- Rewiring MAP kinases in Saccharomyces cerevisiae to regulate novel targets through ubiquitination.eLife · 2016Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic biology applies engineering principles to facilitate the predictable design of biological systems. Biological systems composed of modular parts with clearly defined interactions are generally easier to manipulate than complex systems exhibiting a large number of subtle interactions. However, recreating the function of a naturally complex system with simple modular parts can increase fragility. Here, inspired by scaffold-directed signaling in higher organisms, we modularize prokaryotic signal transduction to allow programmable redirection of phosphate flux from a histidine kinase to response regulators based on targeting by eukaryotic protein-protein interaction domains. Although scaffold-directed colocalization alone was sufficient to direct signaling between components, this minimal system suffered from high sensitivity to changing expression levels of each component. To address this fragility, we demonstrate how to engineer autoinhibition into the kinase so that phosphotransfer is possible only upon binding to the scaffold. This system, in which scaffold performs the dual functions of activating this autoinhibited kinase and directing flux to the cotargeted response regulator, was significantly more robust to varying component concentrations. Thus, we demonstrate that design principles inspired by the complex signal-transduction pathways of eukaryotes may be generalized, abstracted, and applied to prokaryotes using well-characterized parts.
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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.