1. Structural Biology and Molecular Biophysics

Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation

  1. Nicolai Tidemand Johansen
  2. Marta Bonaccorsi
  3. Tone Bengtsen
  4. Andreas Haahr Larsen
  5. Frederik Grønbæk Tidemand
  6. Martin Cramer Pedersen
  7. Pie Huda
  8. Jens Berndtsson
  9. Tamim Darwish
  10. Nageshewar Rao Yepuri
  11. Anne Martel
  12. Thomas Günther Pomorski
  13. Andrea Bertarello
  14. Mark SP Sansom
  15. Mikaela Rapp
  16. Ramon Crehuet
  17. Tobias Schubeis  Is a corresponding author
  18. Kresten Lindorff-Larsen  Is a corresponding author
  19. Guido Pintacuda  Is a corresponding author
  20. Lise Arleth  Is a corresponding author
  1. University of Copenhagen, Denmark
  2. UMR 5280, CNRS, University of Lyon, France
  3. University of Queensland, Australia
  4. Stockholm University, Sweden
  5. Australian Nuclear Science and Technology Organization, Australia
  6. Institut Laue-Langevin, France
  7. University of Oxford, United Kingdom
https://doi.org/10.7554/eLife.71887
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  1. Nicolai Tidemand Johansen
  2. Marta Bonaccorsi
  3. Tone Bengtsen
  4. Andreas Haahr Larsen
  5. Frederik Grønbæk Tidemand
  6. Martin Cramer Pedersen
  7. Pie Huda
  8. Jens Berndtsson
  9. Tamim Darwish
  10. Nageshewar Rao Yepuri
  11. Anne Martel
  12. Thomas Günther Pomorski
  13. Andrea Bertarello
  14. Mark SP Sansom
  15. Mikaela Rapp
  16. Ramon Crehuet
  17. Tobias Schubeis
  18. Kresten Lindorff-Larsen
  19. Guido Pintacuda
  20. Lise Arleth
(2022)
Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation
eLife 11:e71887.
https://doi.org/10.7554/eLife.71887
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Abstract

The CorA family of proteins regulates the homeostasis of divalent metal ions in many bacteria, archaea, and eukaryotic mitochondria, making it an important target in the investigation of the mechanisms of transport and its functional regulation. Although numerous structures of open and closed channels are now available for the CorA family, the mechanism of the transport regulation remains elusive. Here, we investigated the conformational distribution and associated dynamic behaviour of the pentameric Mg2+ channel CorA at room temperature using small-angle neutron scattering (SANS) in combination with molecular dynamics (MD) simulations and solid-state nuclear magnetic resonance spectroscopy (NMR). We find that neither the Mg2+-bound closed structure nor the Mg2+-free open forms are sufficient to explain the average conformation of CorA. Our data support the presence of conformational equilibria between multiple states, and we further find a variation in the behaviour of the backbone dynamics with and without Mg2+. We propose that CorA must be in a dynamic equilibrium between different non-conducting states, both symmetric and asymmetric, regardless of bound Mg2+ but that conducting states become more populated in Mg2+-free conditions. These properties are regulated by backbone dynamics and are key to understanding the functional regulation of CorA.

Data availability

SANS data have been deposited in SASBDB under IDs SASDM42, SASDM52, SASDM62, SASDM72.EM data have been uploaded to the Electron Microscopy Data Bank under IDs EMD-13326 and EMD-13327.Activity (fluorescence) data have been uploaded to GitHub at https://github.com/Niels-Bohr-Institute-XNS-StructBiophys/CorAData/.The Metadynamics simulations have been uploaded to GitHub at https://github.com/KULL-Centre/papers/tree/main/2021/CorA-Johansen-et-al.NMR data have been deposited in Biological Magnetic Resonance Data Bank under ID 50959.

The following data sets were generated

Article and author information

Author details

  1. Nicolai Tidemand Johansen

    Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen E, Denmark
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8596-548X

  2. Marta Bonaccorsi

    Centre de RMN à Très hauts Champs de Lyon, UMR 5280, CNRS, University of Lyon, Villeurbanne, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Tone Bengtsen

    Department of Biology, University of Copenhagen, Copenhagen N, Denmark
    Competing interests
    The authors declare that no competing interests exist.

  4. Andreas Haahr Larsen

    Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen E, Denmark
    Competing interests
    The authors declare that no competing interests exist.

  5. Frederik Grønbæk Tidemand

    Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen E, Denmark
    Competing interests
    The authors declare that no competing interests exist.

  6. Martin Cramer Pedersen

    Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen E, Denmark
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8982-7615

  7. Pie Huda

    Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.

  8. Jens Berndtsson

    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6627-8134

  9. Tamim Darwish

    National Deuteration Facility, Australian Nuclear Science and Technology Organization, Lucas Heights, Australia
    Competing interests
    The authors declare that no competing interests exist.

  10. Nageshewar Rao Yepuri

    National Deuteration Facility, Australian Nuclear Science and Technology Organization, Lucas Heights, Australia
    Competing interests
    The authors declare that no competing interests exist.

  11. Anne Martel

    Institut Laue-Langevin, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.

  12. Thomas Günther Pomorski

    Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark
    Competing interests
    The authors declare that no competing interests exist.

  13. Andrea Bertarello

    Centre de RMN à Très hauts Champs de Lyon, UMR 5280, CNRS, University of Lyon, Villeurbanne, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3705-1760

  14. Mark SP Sansom

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6360-7959

  15. Mikaela Rapp

    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4401-9518

  16. Ramon Crehuet

    Department of Biology, University of Copenhagen, Copenhagen N, Denmark
    Competing interests
    The authors declare that no competing interests exist.

  17. Tobias Schubeis

    Centre de RMN à Très hauts Champs de Lyon, UMR 5280, CNRS, University of Lyon, Villeurbanne, France
    For correspondence
    tobias.schubeis@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.

  18. Kresten Lindorff-Larsen

    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    For correspondence
    lindorff@bio.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4750-6039

  19. Guido Pintacuda

    Centre de RMN à Très hauts Champs de Lyon, UMR 5280, CNRS, University of Lyon, Villeurbanne, France
    For correspondence
    guido.pintacuda@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.

  20. Lise Arleth

    Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
    For correspondence
    arleth@nbi.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4694-4299

Funding

Lundbeckfonden (R155-2015-2666)

  • Kresten Lindorff-Larsen
  • Lise Arleth

European Commission (INFRAIA-01-2018-2019 GA 871037 (iNext Discovery))

  • Tamim Darwish
  • Tobias Schubeis
  • Guido Pintacuda

Villum Fonden (35955)

  • Nicolai Tidemand Johansen
  • Tobias Schubeis
  • Guido Pintacuda

ERC: European Union's Horizon 2020 research and innovation programme (ERC-2015-CoG GA 648974)

  • Guido Pintacuda

Novo Nordisk Fonden (NNF15OC0016670)

  • Lise Arleth

Biotechnology and Biological Sciences Research Council (BB/R00126X/1)

  • Mark SP Sansom

Biotechnology and Biological Sciences Research Council (BB/N000145/1)

  • Mark SP Sansom

Engineering and Physical Sciences Research Council (EP/R004722/1)

  • Mark SP Sansom

Engineering and Physical Sciences Research Council (EP/R029407/1)

  • Mark SP Sansom

Engineering and Physical Sciences Research Council (EP/V010948/1)

  • Mark SP Sansom

Wellcome Trust (208361/Z/17/Z)

  • Mark SP Sansom

National Collaborative Research Infrastructure Strategy (N/A)

  • Tamim Darwish
  • Mark SP Sansom

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Johansen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nicolai Tidemand Johansen
  2. Marta Bonaccorsi
  3. Tone Bengtsen
  4. Andreas Haahr Larsen
  5. Frederik Grønbæk Tidemand
  6. Martin Cramer Pedersen
  7. Pie Huda
  8. Jens Berndtsson
  9. Tamim Darwish
  10. Nageshewar Rao Yepuri
  11. Anne Martel
  12. Thomas Günther Pomorski
  13. Andrea Bertarello
  14. Mark SP Sansom
  15. Mikaela Rapp
  16. Ramon Crehuet
  17. Tobias Schubeis
  18. Kresten Lindorff-Larsen
  19. Guido Pintacuda
  20. Lise Arleth
(2022)
Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation
eLife 11:e71887.
https://doi.org/10.7554/eLife.71887

Share this article

https://doi.org/10.7554/eLife.71887

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