ArticleScience (New York, N.Y.)2019
De novo design of tunable, pH-driven conformational changes.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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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.
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Who cites it
79 citing papers in PubMed.
- Trial
- Deep learning based design of buried hydrogen bond networks with HBDesigner.bioRxiv : the preprint server for biology · 2026Article
- A histidine switch controls the pH-responsive self-assembly of a helical protein filament.bioRxiv : the preprint server for biology · 2026Article
- Circular RNA-mediated regulation of key signaling pathways in cardiovascular diseases: a review.Journal of advanced research · 2026Review
- Review
- De novo protein design: a transformative frontier in clinical protein applications.Journal of translational medicine · 2026Review
- Sequence Prediction, Structural Modelling and the Challenges of Plasticity in Coiled Coils.Sub-cellular biochemistry · 2026Review
- Construction of artificial organellesChemical science · 2025Review
- De novo design of light-responsive protein-protein interactions enables reversible formation of protein assemblies.Nature chemistry · 2025Article
- Bond-centric modular design of protein assemblies.Nature materials · 2025Article
- Computational design of pH-sensitive binders.bioRxiv : the preprint server for biology · 2025Article
- Molecular circuits for genomic recording of cellular events.Trends in genetics : TIG · 2025Review
- A De Novo Designed Metalloprotein Displays Variable Thermal Stability and Binding Stoichiometry with Transition Metal Ions.Chembiochem : a European journal of chemical biology · 2025Article
- Engineered single chain variable fragments (scFvs) with improved pH-dependent kinetics for use in continuous biosensor applications.RSC advances · 2025Article
- Article
- A Designed ZnJournal of the American Chemical Society · 2025Article
- Transforming an ATP-dependent enzyme into a dissipative, self-assembling system.Nature chemical biology · 2025Article
- Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints.Journal of chemical theory and computation · 2025Article
- Seesaw protein: Design of a protein that adopts interconvertible alternative functional conformations and its dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.ACS nano · 2025Article
19 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
21 authors.
Funding
Abstract
The ability of naturally occurring proteins to change conformation in response to environmental changes is critical to biological function. Although there have been advances in the de novo design of stable proteins with a single, deep free-energy minimum, the design of conformational switches remains challenging. We present a general strategy to design pH-responsive protein conformational changes by precisely preorganizing histidine residues in buried hydrogen-bond networks. We design homotrimers and heterodimers that are stable above pH 6.5 but undergo cooperative, large-scale conformational changes when the pH is lowered and electrostatic and steric repulsion builds up as the network histidine residues become protonated. The transition pH and cooperativity can be controlled through the number of histidine-containing networks and the strength of the surrounding hydrophobic interactions. Upon disassembly, the designed proteins disrupt lipid membranes both in vitro and after being endocytosed in mammalian cells. Our results demonstrate that environmentally triggered conformational changes can now be programmed by de novo protein design.
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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.