ArticleStructure (London, England : 1993)2012
Mutational tipping points for switching protein folds and functions.
Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Signatures of protein fold switching in the unfolded state.Biophysical journal · 2026Article
- Fold-Switching Proteins.Annual review of biophysics · 2026Review
- Article
- Morpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes.Bioinformatics (Oxford, England) · 2025Article
- On the emergence of metabolism: the evolution of proteins that powered life.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Fold-switching proteins.ArXiv · 2025Article
- Statistical Thermodynamics of the Protein Ensemble: Mediating Function and Evolution.Annual review of biophysics · 2025Review
- AlphaFold2's training set powers its predictions of some fold-switched conformations.Protein science : a publication of the Protein Society · 2025Article
- Leveraging Sequence Purification for Accurate Prediction of Multiple Conformational States with AlphaFold2.Research square · 2025Article
- Aromatic-aromatic interactions drive fold switch of GA95 and GB95 with three residue difference.Chemical science · 2025Article
- Chameleon sequences-Structural effects.PloS one · 2025Article
- High fitness paths can connect proteins with low sequence overlap.bioRxiv : the preprint server for biology · 2024Article
- Article
- AlphaFold2's training set powers its predictions of fold-switched conformations.bioRxiv : the preprint server for biology · 2024Article
- Chameleon Sequences-Structural Effects in Proteins Characterized by Hydrophobicity Disorder.ACS omega · 2024Article
- Ancestral Reconstruction and the Evolution of Protein Energy Landscapes.Annual review of biophysics · 2024Review
- Article
- 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
- Simulations of a protein fold switch reveal crowding-induced population shifts driven by disordered regions.Communications chemistry · 2023Article
5 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
While disordered to ordered rearrangements are relatively common, the ability of proteins to switch from one ordered fold to a completely different fold is generally regarded as rare, and few fold switches have been characterized. Here, in a designed system, we examine the mutational requirements for transitioning between folds and functions. We show that switching between monomeric 3α and 4β+α folds can occur in multiple ways with successive single amino acid changes at diverse residue positions, raising the likelihood that such transitions occur in the evolution of new folds. Even mutations on the periphery of the core can tip the balance between alternatively folded states. Ligand-binding studies illustrate that a new immunoglobulin G-binding function can be gained well before the relevant 4β+α fold is appreciably populated in the unbound protein. The results provide new insights into the evolution of fold and function.
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