ArticleNature communications2023
Identification of a covert evolutionary pathway between two protein folds.
Article in Nature communications, 2023. 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, 33 citations in OpenAlex.
- Fold-Switching Proteins.Annual review of biophysics · 2026Review
- Wanted: A population genetic theory of biological noise regulation.PLoS genetics · 2026Article
- Piecing Together the History of Protein Folds From a Fragmented Evolutionary Record.Genome biology and evolution · 2025Article
- Fold-switching proteins.ArXiv · 2025Article
- DivPro: diverse protein sequence design with direct structure recovery guidance.Bioinformatics (Oxford, England) · 2025Article
- Origin and Evolution of Bacterial Periplasmic Force Transducers.Molecular biology and evolution · 2025Article
- Genetic Variation and Gene Expression of the Antimicrobial Peptide Macins in Asian Buffalo Leech (Biology · 2025Article
- Evolving concepts of the protein universe.iScience · 2025Review
- Proteins with alternative folds reveal blind spots in AlphaFold-based protein structure prediction.Current opinion in structural biology · 2025Review
- Aromatic-aromatic interactions drive fold switch of GA95 and GB95 with three residue difference.Chemical science · 2025Article
- High fitness paths can connect proteins with low sequence overlap.bioRxiv : the preprint server for biology · 2024Article
- Article
- Proteins with alternative folds reveal blind spots in AlphaFold-based protein structure prediction.ArXiv · 2024Article
- Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.International journal of molecular sciences · 2024Article
- An ancestral fold reveals the evolutionary link between RNA polymerase and ribosomal proteins.Nature communications · 2024Article
- The ancient Z-DNA and Z-RNA specific Zα fold has evolved modern roles in immunity and transcription through the natural selection of flipons.Royal Society open science · 2024Article
- The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm?Protein science : a publication of the Protein Society · 2024Article
- 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
- Evolutionary selection of proteins with two folds.Nature communications · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Although homologous protein sequences are expected to adopt similar structures, some amino acid substitutions can interconvert α-helices and β-sheets. Such fold switching may have occurred over evolutionary history, but supporting evidence has been limited by the: (1) abundance and diversity of sequenced genes, (2) quantity of experimentally determined protein structures, and (3) assumptions underlying the statistical methods used to infer homology. Here, we overcome these barriers by applying multiple statistical methods to a family of ~600,000 bacterial response regulator proteins. We find that their homologous DNA-binding subunits assume divergent structures: helix-turn-helix versus α-helix + β-sheet (winged helix). Phylogenetic analyses, ancestral sequence reconstruction, and AlphaFold2 models indicate that amino acid substitutions facilitated a switch from helix-turn-helix into winged helix. This structural transformation likely expanded DNA-binding specificity. Our approach uncovers an evolutionary pathway between two protein folds and provides a methodology to identify secondary structure switching in other protein families.
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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.