ArticleNature2019
De novo design of bioactive protein switches.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed.
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- ESMDynamic: Fast and accurate prediction of protein dynamic contact maps from single sequences.Nature communications · 2026Article
- Opportunities for artificial intelligence and synthetic biology in designing living drug delivery systems.Advanced drug delivery reviews · 2026Review
- Deep Learning Predicts Dissimilar DNA-DNA Binding and Engineers Hyperconnected Networks.Nature communications · 2026Article
- Modular Input-Output Biosensor Design UsingACS sensors · 2026Article
- Modeling Reveals How Direct-Acting Antivirals Redirect HBV Capsid Assembly Pathways to Noninfectious Products.bioRxiv : the preprint server for biology · 2026Article
- Negative design enables cell-free expression and folding of designed transmembrane β-barrels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- De novo protein design: a transformative frontier in clinical protein applications.Journal of translational medicine · 2026Review
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- The Current Landscape of Modular CAR T Cells.International journal of molecular sciences · 2025Review
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Protein A-like peptide generation based on generalized diffusion model.Journal of computer-aided molecular design · 2025Article
- Computationally Designed Nanobinders as Affinity Ligands in Diagnostic and Therapeutic Applications.Journal of the American Chemical Society · 2025Article
- De novo designed protein guiding targeted protein degradation.Nature communications · 2025Article
- Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.Experimental hematology & oncology · 2025Review
- Evolutionary regulation of human Fas ligand (CD95L) by plasmin in solid cancer immunotherapy.Nature communications · 2025Article
- A Designed ZnJournal of the American Chemical Society · 2025Article
- Deep learning-guided design of dynamic proteins.Science (New York, N.Y.) · 2025Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering.
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Identifiers
What OpenQuestion holds
Registered trials
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.