ArticleProceedings of the National Academy of Sciences of the United States of America2014
Intrinsic disorder as a generalizable strategy for the rational design of highly responsive, allosterically cooperative receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 77 citations in OpenAlex.
- Engineering modular and tunable single-molecule sensors by decoupling sensing from signal output.Nature nanotechnology · 2025Article
- Controlled mechanochemical coupling of anti-junctions in DNA origami arrays.Nature communications · 2024Article
- On the Rational Design of Cooperative Receptors.Annual review of biophysics · 2023Review
- Functional advantages of building nanosystems using multiple molecular components.Nature chemistry · 2023Article
- The sequestration mechanism as a generalizable approach to improve the sensitivity of biosensors and bioassays.Chemical science · 2022Article
- Engineering and exploiting synthetic allostery of NanoLuc luciferase.Nature communications · 2022Article
- The Nature of Noradrenergic Volume Transmission From Locus Coeruleus to Brainstem Mesencephalic Trigeminal Sensory Neurons.Frontiers in cellular neuroscience · 2022Article
- Single antibody detection in a DNA origami nanoantenna.iScience · 2021Article
- pH-Responsive DNA Motif: From Rational Design to Analytical Applications.Frontiers in chemistry · 2021Review
- Thermodynamic analysis of cooperative ligand binding by the ATP-binding DNA aptamer indicates a population-shift binding mechanism.Scientific reports · 2020Article
- Rational design to control the trade-off between receptor affinity and cooperativity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Re-Evaluating the Conventional Wisdom about Binding Assays.Trends in biochemical sciences · 2020Review
- Manipulating the hydrophobicity of DNA as a universal strategy for visual biosensing.Nature protocols · 2020Article
- Innovative engineering and sensing strategies for aptamer-based small-molecule detection.Trends in analytical chemistry : TRAC · 2019Article
- Single-step multivalent capture assay for nucleic acid detection with dual-affinity regulation using mutation inhibition and allosteric activation.Chemical science · 2019Article
- Electrochemical DNA-Based Sensors for Molecular Quality Control: Continuous, Real-Time Melamine Detection in Flowing Whole Milk.Analytical chemistry · 2018Article
- Introducing structure-switching functionality into small-molecule-binding aptamers via nuclease-directed truncation.Nucleic acids research · 2018Article
- First characterization of a biphasic, switch-like DNA amplification.The Analyst · 2018Article
- Sensitive Detection of Small-Molecule Targets Using Cooperative Binding Split Aptamers and Enzyme-Assisted Target Recycling.Analytical chemistry · 2018Article
- Real-time measurement of small molecules directly in awake, ambulatory animals.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Control over the sensitivity with which biomolecular receptors respond to small changes in the concentration of their target ligand is critical for the proper function of many cellular processes. Such control could likewise be of utility in artificial biotechnologies, such as biosensors, genetic logic gates, and "smart" materials, in which highly responsive behavior is of value. In nature, the control of molecular responsiveness is often achieved using "Hill-type" cooperativity, a mechanism in which sequential binding events on a multivalent receptor are coupled such that the first enhances the affinity of the next, producing a steep, higher-order dependence on target concentration. Here, we use an intrinsic-disorder-based mechanism that can be implemented without requiring detailed structural knowledge to rationally introduce this potentially useful property into several normally noncooperative biomolecules. To do so, we fabricate a tandem repeat of the receptor that is destabilized (unfolded) via the introduction of a long, unstructured loop. The first binding event requires the energetically unfavorable closing of this loop, reducing its affinity relative to that of the second binding event, which, in contrast occurs at a preformed site. Using this approach, we have rationally introduced cooperativity into three unrelated DNA aptamers, achieving in the best of these a Hill coefficient experimentally indistinguishable from the theoretically expected maximum. The extent of cooperativity and thus the steepness of the binding transition are, moreover, well modeled as simple functions of the energetic cost of binding-induced folding, speaking to the quantitative nature of this design strategy.
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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.