ArticleProceedings of the National Academy of Sciences of the United States of America2021
Structural dynamics in the evolution of a bilobed protein scaffold.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
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- Optimizing Stability in Dynamic Small-Molecule Binding Proteins.Journal of the American Chemical Society · 2026Article
- Development of a small compound that regulates the function of a maltodextrin-binding protein of Streptococcus pyogenes by multifaceted screenings.Scientific reports · 2025Article
- Labelizer: systematic selection of protein residues for covalent fluorophore labeling.Nature communications · 2025Article
- Lipid rafts: novel therapeutic targets for metabolic, neurodegenerative, oncological, and cardiovascular diseases.Lipids in health and disease · 2025Review
- From duplication to fusion: Expanding Dayhoff's model of protein evolution.Protein science : a publication of the Protein Society · 2025Review
- The Multifunctional Preprotein Binding Domain of SecA.Chembiochem : a European journal of chemical biology · 2024Article
- Hybrid Exb/Mot stators require substitutions distant from the chimeric pore to power flagellar rotation.Journal of bacteriology · 2024Article
- How arginine inhibits substrate-binding domain 2 elucidated using molecular dynamics simulations.Protein science : a publication of the Protein Society · 2024Article
- Conflicting Interfacial Electrostatic Interactions as a Design Principle to Modulate Long-Range Interdomain Communication.ACS bio & med chem Au · 2024Article
- Retracing the evolution of a modern periplasmic binding protein.Protein science : a publication of the Protein Society · 2023Article
- The role of oligomerization in the optimization of cyclohexadienyl dehydratase conformational dynamics and catalytic activity.Protein science : a publication of the Protein Society · 2022Article
- Computational Docking Reveals Co-Evolution of C4 Carbon Delivery Enzymes in Diverse Plants.International journal of molecular sciences · 2022Article
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel biophysical tools allow the structural dynamics of proteins and the regulation of such dynamics by binding partners to be explored in unprecedented detail. Although this has provided critical insights into protein function, the means by which structural dynamics direct protein evolution remain poorly understood. Here, we investigated how proteins with a bilobed structure, composed of two related domains from the periplasmic-binding protein-like II domain family, have undergone divergent evolution, leading to adaptation of their structural dynamics. We performed a structural analysis on ∼600 bilobed proteins with a common primordial structural core, which we complemented with biophysical studies to explore the structural dynamics of selected examples by single-molecule Förster resonance energy transfer and Hydrogen-Deuterium exchange mass spectrometry. We show that evolutionary modifications of the structural core, largely at its termini, enable distinct structural dynamics, allowing the diversification of these proteins into transcription factors, enzymes, and extracytoplasmic transport-related proteins. Structural embellishments of the core created interdomain interactions that stabilized structural states, reshaping the active site geometry, and ultimately altered substrate specificity. Our findings reveal an as-yet-unrecognized mechanism for the emergence of functional promiscuity during long periods of evolution and are applicable to a large number of domain architectures.
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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.