ArticleProceedings of the National Academy of Sciences of the United States of America2023
Reversible switching between two common protein folds in a designed system using only temperature.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Fold-Switching Proteins.Annual review of biophysics · 2026Review
- Article
- Article
- Morpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes.Bioinformatics (Oxford, England) · 2025Article
- Proteome-wide identification of metamorphic protein candidates using mass spectrometry.bioRxiv : the preprint server for biology · 2025Article
- The Ensemble Basis of Allostery and Function: Insights from Models of Local Unfolding.Journal of molecular biology · 2025Review
- Fold-switching proteins.ArXiv · 2025Article
- Conformational dynamics and multimodal interaction of Paxillin with the focal adhesion targeting domain.Science advances · 2025Article
- Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain.bioRxiv : the preprint server for biology · 2025Article
- Unveiling the cold reality of metamorphic proteins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Evolving concepts of the protein universe.iScience · 2025Review
- AFsample2 predicts multiple conformations and ensembles with AlphaFold2.Communications biology · 2025Article
- Photocontrolling the Enantioselectivity of a Phosphotriesterase via Incorporation of a Light-Responsive Unnatural Amino Acid.JACS Au · 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
- Temperature-dependent fold-switching mechanism of the circadian clock protein KaiB.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- AlphaFold predictions of fold-switched conformations are driven by structure memorization.Nature communications · 2024Article
- An ancestral fold reveals the evolutionary link between RNA polymerase and ribosomal proteins.Nature communications · 2024Article
- AlphaFold2 has more to learn about protein energy landscapes.bioRxiv : the preprint server for biology · 2023Article
- SSDraw: Software for generating comparative protein secondary structure diagrams.Protein science : a publication of the Protein Society · 2023Article
- SSDraw: software for generating comparative protein secondary structure diagrams.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Naturally occurring metamorphic proteins have the ability to interconvert from one folded state to another through either a limited set of mutations or by way of a change in the local environment. Here, we show in a designed system that it is possible to switch reversibly between two of the most common monomeric folds employing only temperature changes. We demonstrate that a latent 3α state can be unmasked from an α/β-plait topology with a single V90T amino acid substitution, populating both forms simultaneously. The equilibrium between these two states exhibits temperature dependence, such that the 3α state is predominant (>90%) at 5 °C, while the α/β-plait fold is the major species (>90%) at 30 °C. We describe the structure and dynamics of these topologies, how mutational changes affect the temperature dependence, and the energetics and kinetics of interconversion. Additionally, we demonstrate how ligand-binding function can be tightly regulated by large amplitude changes in protein structure over a relatively narrow temperature range that is relevant to biology. The 3α/αβ switch thus represents a potentially useful approach for designing proteins that alter their fold topologies in response to environmental triggers. It may also serve as a model for computational studies of temperature-dependent protein stability and fold switching.
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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.