ArticleProceedings of the National Academy of Sciences of the United States of America2022
Creative destruction: New protein folds from old.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed.
- Systematic discovery of circular permutations across the protein universe using CIRPIN.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Borderlands of Foldability: Lessons from Simplified Proteins.Trends in chemistry · 2026Article
- Protein folds and catalytic strategies at the origin of biological CO2 fixation.FEMS microbiology ecology · 2026Article
- Origin of class B J-domain proteins involved in amyloid transactions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rapid discovery of new-to-nature protein domains by novelty-first forcing of language models.bioRxiv : the preprint server for biology · 2025Article
- Accurate detection of tandem repeats exposes ubiquitous reuse of biological sequences.Nucleic acids research · 2025Article
- Protein Structural Phylogenetics.Genome biology and evolution · 2025Review
- Piecing Together the History of Protein Folds From a Fragmented Evolutionary Record.Genome biology and evolution · 2025Article
- Advancing Molecular Simulations: Merging Physical Models, Experiments, and AI to Tackle Multiscale Complexity.The journal of physical chemistry letters · 2025Review
- Chemical Evolution of Life on Earth.Genes · 2025Review
- High fitness paths can connect proteins with low sequence overlap.bioRxiv : the preprint server for biology · 2024Article
- Article
- Deep generative models of protein structure uncover distant relationships across a continuous fold space.Nature communications · 2024Article
- An ancestral fold reveals the evolutionary link between RNA polymerase and ribosomal proteins.Nature communications · 2024Article
- Amino-Acid Characteristics in Protein Native State Structures.Biomolecules · 2024Article
- Selection of a promiscuous minimalist cAMP phosphodiesterase from a library of de novo designed proteins.Nature chemistry · 2024Article
- Retracing the evolution of a modern periplasmic binding protein.Protein science : a publication of the Protein Society · 2023Article
- Fluid protein fold space and its implications.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Identification of a covert evolutionary pathway between two protein folds.Nature communications · 2023Article
- Introducing creative destruction as a mechanism in protein evolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Mechanisms of emergence and divergence of protein folds pose central questions in biological sciences. Incremental mutation and stepwise adaptation explain relationships between topologically similar protein folds. However, the universe of folds is diverse and riotous, suggesting more potent and creative forces are at play. Sequence and structure similarity are observed between distinct folds, indicating that proteins with distinct folds may share common ancestry. We found evidence of common ancestry between three distinct β-barrel folds: Scr kinase family homology (SH3), oligonucleotide/oligosaccharide-binding (OB), and cradle loop barrel (CLB). The data suggest a mechanism of fold evolution that interconverts SH3, OB, and CLB. This mechanism, which we call creative destruction, can be generalized to explain many examples of fold evolution including circular permutation. In creative destruction, an open reading frame duplicates or otherwise merges with another to produce a fused polypeptide. A merger forces two ancestral domains into a new sequence and spatial context. The fused polypeptide can explore folding landscapes that are inaccessible to either of the independent ancestral domains. However, the folding landscapes of the fused polypeptide are not fully independent of those of the ancestral domains. Creative destruction is thus partially conservative; a daughter fold inherits some motifs from ancestral folds. After merger and refolding, adaptive processes such as mutation and loss of extraneous segments optimize the new daughter fold. This model has application in disease states characterized by genetic instability. Fused proteins observed in cancer cells are likely to experience remodeled folding landscapes and realize altered folds, conferring new or altered functions.
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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 Socratic graph.