ArticleACS chemical biology2008
A Ca2+-sensing molecular switch based on alternate frame protein folding.
Article in ACS chemical biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Structure Prediction of Alternate Frame Folding Systems with AlphaFold3.Journal of chemical information and modeling · 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
- Enhancing response of a protein conformational switch by using two disordered ligand binding domains.Frontiers in molecular biosciences · 2023Article
- Engineering protein activity into off-the-shelf DNA devices.Cell reports methods · 2022Article
- Engineering a Fluorescent Protein Color Switch Using Entropy-Driven β-Strand Exchange.ACS sensors · 2022Article
- Engineering protein and DNA tools for creating DNA-dependent protein switches.Methods in enzymology · 2022Article
- The Next Frontier for Designing Switchable Proteins: Rational Enhancement of Kinetics.The journal of physical chemistry. B · 2021Article
- The RED scheme: Rate-constant estimation from pre-steady state weighted ensemble simulations.The Journal of chemical physics · 2021Article
- Large enhancement of response times of a protein conformational switch by computational design.Nature communications · 2018Article
- Small Molecule-Induced Domain Swapping as a Mechanism for Controlling Protein Function and Assembly.Scientific reports · 2017Article
- Construction of Allosteric Protein Switches by Alternate Frame Folding and Intermolecular Fragment Exchange.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Influence of Secondary-Structure Folding on the Mutually Exclusive Folding Process of GL5/I27 Protein: Evidence from Molecular Dynamics Simulations.International journal of molecular sciences · 2016Article
- Converting a binding protein into a biosensing conformational switch using protein fragment exchange.Biochemistry · 2014Article
- Thermodynamic basis for engineering high-affinity, high-specificity binding-induced DNA clamp nanoswitches.ACS nano · 2013Article
- GFP variants with alternative β-strands and their application as light-driven protease sensors: a tale of two tails.Journal of the American Chemical Society · 2013Article
- Regulated unfolding of proteins in signaling.FEBS letters · 2013Review
- Stepwise conversion of a binding protein to a fluorescent switch: application to Thermoanaerobacter tengcongensis ribose binding protein.Biochemistry · 2013Article
- Protein conformational switches: from nature to design.Chemistry (Weinheim an der Bergstrasse, Germany) · 2012Review
- Engineering biosensors with extended, narrowed, or arbitrarily edited dynamic range.Journal of the American Chemical Society · 2012Article
- Structural characterization of two alternate conformations in a calbindin D₉k-based molecular switch.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Existing strategies for creating biosensors mainly rely on large conformational changes to transduce a binding event to an output signal. Most molecules, however, do not exhibit large-scale structural changes upon substrate binding. Here, we present a general approach (alternate frame folding, or AFF) for engineering allosteric control into ligand binding proteins. AFF can in principle be applied to any protein to establish a binding-induced conformational change, even if none exists in the natural molecule. The AFF design duplicates a portion of the amino acid sequence, creating an additional "frame" of folding. One frame corresponds to the wild-type sequence, and folding produces the normal structure. Folding in the second frame yields a circularly permuted protein. Because the two native structures compete for a shared sequence, they fold in a mutually exclusive fashion. Binding energy is used to drive the conformational change from one fold to the other. We demonstrate the approach by converting the protein calbindin D(9k) into a molecular switch that senses Ca2+. The structures of Ca2+-free and Ca2+-bound calbindin are nearly identical. Nevertheless, the AFF mechanism engineers a robust conformational change that we detect using two covalently attached fluorescent groups. Biological fluorophores can also be employed to create a genetically encoded sensor. AFF should be broadly applicable to create sensors for a variety of small molecules.
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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.