Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation
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 channe...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/71887 |
| _version_ | 1811201586561548288 |
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| author | Nicolai Tidemand Johansen Marta Bonaccorsi Tone Bengtsen Andreas Haahr Larsen Frederik Grønbæk Tidemand Martin Cramer Pedersen Pie Huda Jens Berndtsson Tamim Darwish Nageshewar Rao Yepuri Anne Martel Thomas Günther Pomorski Andrea Bertarello Mark Sansom Mikaela Rapp Ramon Crehuet Tobias Schubeis Kresten Lindorff-Larsen Guido Pintacuda Lise Arleth |
| author_facet | Nicolai Tidemand Johansen Marta Bonaccorsi Tone Bengtsen Andreas Haahr Larsen Frederik Grønbæk Tidemand Martin Cramer Pedersen Pie Huda Jens Berndtsson Tamim Darwish Nageshewar Rao Yepuri Anne Martel Thomas Günther Pomorski Andrea Bertarello Mark Sansom Mikaela Rapp Ramon Crehuet Tobias Schubeis Kresten Lindorff-Larsen Guido Pintacuda Lise Arleth |
| author_sort | Nicolai Tidemand Johansen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:24:09Z |
| format | Article |
| id | doaj.art-3958a7b65ed7431d8436567fd3a41ae6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:24:09Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3958a7b65ed7431d8436567fd3a41ae62022-12-22T03:52:02ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.71887Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulationNicolai Tidemand Johansen0https://orcid.org/0000-0002-8596-548XMarta Bonaccorsi1https://orcid.org/0000-0001-6177-0701Tone Bengtsen2https://orcid.org/0000-0001-8423-2156Andreas Haahr Larsen3https://orcid.org/0000-0002-2230-2654Frederik Grønbæk Tidemand4https://orcid.org/0000-0001-8914-9626Martin Cramer Pedersen5https://orcid.org/0000-0002-8982-7615Pie Huda6https://orcid.org/0000-0002-2197-4993Jens Berndtsson7https://orcid.org/0000-0001-6627-8134Tamim Darwish8https://orcid.org/0000-0001-7704-1837Nageshewar Rao Yepuri9https://orcid.org/0000-0002-4665-1306Anne Martel10Thomas Günther Pomorski11https://orcid.org/0000-0002-4889-0829Andrea Bertarello12https://orcid.org/0000-0003-3705-1760Mark Sansom13https://orcid.org/0000-0001-6360-7959Mikaela Rapp14https://orcid.org/0000-0002-4401-9518Ramon Crehuet15https://orcid.org/0000-0002-6687-382XTobias Schubeis16https://orcid.org/0000-0003-2203-1126Kresten Lindorff-Larsen17https://orcid.org/0000-0002-4750-6039Guido Pintacuda18https://orcid.org/0000-0001-7757-2144Lise Arleth19https://orcid.org/0000-0002-4694-4299Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen, DenmarkCentre de RMN à Très hauts Champs de Lyon (UMR 5280, CNRS / Ecole Normale Supérieure de Lyon / Université Claude Bernard Lyon 1), University of Lyon, Villeurbanne, FranceStructural Biology and NMR Laboratory and Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, University of Oxford, Oxford, United KingdomCondensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, University of Oxford, Oxford, United KingdomCondensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen, DenmarkCondensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen, DenmarkAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, AustraliaDepartment of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, Stockholm, SwedenNational Deuteration Facility, Australian Nuclear Science and Technology Organization, Lucas Heights, AustraliaNational Deuteration Facility, Australian Nuclear Science and Technology Organization, Lucas Heights, AustraliaInstitut Laue–Langevin, Grenoble, FranceSection for Transport Biology, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark; Department of Molecular Biochemistry, Faculty of Chemistry and Biochemistry, Ruhr University, Bochum, GermanyCentre de RMN à Très hauts Champs de Lyon (UMR 5280, CNRS / Ecole Normale Supérieure de Lyon / Université Claude Bernard Lyon 1), University of Lyon, Villeurbanne, FranceDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, Stockholm, SwedenStructural Biology and NMR Laboratory and Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark; CSIC-Institute for Advanced Chemistry of Catalonia (IQAC), Barcelona, SpainCentre de RMN à Très hauts Champs de Lyon (UMR 5280, CNRS / Ecole Normale Supérieure de Lyon / Université Claude Bernard Lyon 1), University of Lyon, Villeurbanne, FranceStructural Biology and NMR Laboratory and Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, DenmarkCentre de RMN à Très hauts Champs de Lyon (UMR 5280, CNRS / Ecole Normale Supérieure de Lyon / Université Claude Bernard Lyon 1), University of Lyon, Villeurbanne, FranceCondensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Copenhagen, DenmarkThe 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.https://elifesciences.org/articles/71887cora mg2+ channelsmall-angle neutron scatteringsolid-state nuclear magnetic resonancemetadynamics simulation |
| spellingShingle | Nicolai Tidemand Johansen Marta Bonaccorsi Tone Bengtsen Andreas Haahr Larsen Frederik Grønbæk Tidemand Martin Cramer Pedersen Pie Huda Jens Berndtsson Tamim Darwish Nageshewar Rao Yepuri Anne Martel Thomas Günther Pomorski Andrea Bertarello Mark Sansom Mikaela Rapp Ramon Crehuet Tobias Schubeis Kresten Lindorff-Larsen Guido Pintacuda Lise Arleth Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation eLife cora mg2+ channel small-angle neutron scattering solid-state nuclear magnetic resonance metadynamics simulation |
| title | Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation |
| title_full | Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation |
| title_fullStr | Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation |
| title_full_unstemmed | Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation |
| title_short | Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation |
| title_sort | mg2 dependent conformational equilibria in cora and an integrated view on transport regulation |
| topic | cora mg2+ channel small-angle neutron scattering solid-state nuclear magnetic resonance metadynamics simulation |
| url | https://elifesciences.org/articles/71887 |
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