Evidence map›Paper›PMID 34845009›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Structural dynamics in the evolution of a bilobed protein scaffold.

Giorgos Gouridis, Yusran A Muthahari, Marijn de Boer, Douglas A Griffith, Alexandra Tsirigotaki, Konstantinos Tassis, Niels Zijlstra, Ruixue Xu, Nikolaos Eleftheriadis, Yovin Sugijo and 6 more

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Optimizing Stability in Dynamic Small-Molecule Binding Proteins.Journal of the American Chemical Society · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. From duplication to fusion: Expanding Dayhoff's model of protein evolution.Protein science : a publication of the Protein Society · 2025
    Review
  8. The Multifunctional Preprotein Binding Domain of SecA.Chembiochem : a European journal of chemical biology · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Retracing the evolution of a modern periplasmic binding protein.Protein science : a publication of the Protein Society · 2023
    Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 4 countries.

Giorgos GouridisPhysical and Synthetic Biology, Faculty of Biology, Ludwig Maximilians-Universität München, Planegg-Martinsried 82152, Germany; g.gouridis@imbb.forth.gr cordes@bio.lmu.de.ORCID 0000-0002-2255-0455
Yusran A MuthahariMolecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Groningen 9747 AG, The Netherlands.ORCID 0000-0002-9705-0586
Marijn de BoerMolecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Groningen 9747 AG, The Netherlands.
Douglas A GriffithPhysical and Synthetic Biology, Faculty of Biology, Ludwig Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
Alexandra TsirigotakiLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven 3000, Belgium.
Konstantinos TassisMolecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Groningen 9747 AG, The Netherlands.
Niels ZijlstraPhysical and Synthetic Biology, Faculty of Biology, Ludwig Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
Ruixue XuLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven 3000, Belgium.
Nikolaos EleftheriadisMolecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Groningen 9747 AG, The Netherlands.ORCID 0000-0002-1738-6419
Yovin SugijoMolecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Groningen 9747 AG, The Netherlands.ORCID 0000-0003-0514-6968
Martin ZachariasTheoretical Biophysics, Physics Department, Technical University of Munich, Garching 85748, Germany.ORCID 0000-0001-5163-2663
Alexander DömlingDrug Design Group, Department of Pharmacy, University of Groningen, Groningen 9713 AV, The Netherlands.
Spyridoula KaramanouLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven 3000, Belgium.ORCID 0000-0002-8803-1404
Charalambos PozidisStructural Biology Division, Institute of Molecular Biology and Biotechnology, Heraklion-Crete 70013, Greece.
Anastassios EconomouLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven 3000, Belgium.ORCID 0000-0002-1770-507X
Thorben CordesPhysical and Synthetic Biology, Faculty of Biology, Ludwig Maximilians-Universität München, Planegg-Martinsried 82152, Germany; g.gouridis@imbb.forth.gr cordes@bio.lmu.de.ORCID 0000-0002-8598-5499
University of Groningen · NLRega Institute for Medical Research · BELudwig-Maximilians-Universität München · DEFORTH Institute of Molecular Biology and Biotechnology · GRTechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Escherichia coliEvolution, MolecularGene Expression RegulationMass SpectrometryModels, MolecularPhylogenyProtein ConformationProtein DomainsProteinsProteinsbiophysicsevolutionligand bindingprotein structurestructural dynamics

Identifiers

PMID34845009
PMCPMC8694067
OpenAlexW3217192246

What OpenQuestion holds

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Registered trials

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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.