Functional roles of Mg2+ binding sites in ion-dependent gating of a Mg2+ channel, MgtE, revealed by solution NMR
Open accessAbstract
Magnesium ions (Mg2+) are divalent cations essential for various cellular functions. Mg2+ homeostasis is maintained through Mg2+ channels such as MgtE, a prokaryotic Mg2+ channel whose gating is regulated by intracellular Mg2+ levels. Our previous crystal structure of MgtE in the Mg2+-bound, closed state revealed the existence of seven crystallographically-independent Mg2+-binding sites, Mg1–Mg7. The role of Mg2+-binding to each site in channel closure remains unknown. Here, we investigated Mg2+-dependent changes in the structure and dynamics of MgtE using nuclear magnetic resonance spectroscopy. Mg2+-titration experiments, using wild-type and mutant forms of MgtE, revealed that the Mg2+ binding sites Mg1, Mg2, Mg3, and Mg6, exhibited cooperativity and a higher affinity for Mg2+, enabling the remaining Mg2+ binding sites, Mg4, Mg5, and Mg7, to play important roles in channel closure. This study revealed the role of each Mg2+-binding site in MgtE gating, underlying the mechanism of cellular Mg2+ homeostasis.
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MgtE functions as a Mg2+-gated channel and is feedback inhibited when intracellular Mg2+ reaches ~4 mM and binds to several cytoplasmic sensing sites.
“MgtE functions as a Mg2+-gated channel and is also feedback inhibited when intracellular Mg2+ reaches ∼4 mM and binds to several cytoplasmic sensing sites.74,75”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [75]
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Began, J., Cordier, B., Březinová, J., Delisle, J., Hexnerová, R., Srb, P., Rampírová, P., Kožíšek, M., Baudet, M., Couté, Y., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019102935 · Cited by 55 · see citing works
Metals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
- Authors
- Maruyama, T., Imai, S., Kusakizako, T., Hattori, M., Ishitani, R., Nureki, O., Ito, K., Maturana, A. D., Shimada, I., & Osawa, M.
- Affiliations
- The University of Tokyo (JP)
- Fudan University (CN)
- Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
- Keio University (JP)
- Corresponding author
- Shimada, Ichio
- Osawa, Masanori
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-04-03
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5882242
- OpenAlex
- W2796394067
- Cited by
- 17
- References
- 1
- Citations by year
- 2025: 6 · 2023: 1 · 2022: 5 · 2020: 2 · 2019: 2 · 2018: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- New Energy and Industrial Technology Development Organization
- Ministry of Economy, Trade and Industry
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science, and Technology
- Japan Society for the Promotion of Science (KAKENHI JP16H01368, KAKENHI JP17H03978)
- Vehicle Racing Commemorative Foundation
- SENSHIN Medical Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Nursing › Nutrition and Dietetics › Magnesium in Health and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- MgTe, magnesium channel, Mg2+ binding site, channel closure, cooperativity, divalent cation binding, prokaryotic ion channels, solution NMR
- MeSH terms
- Bacterial Proteins, Binding Sites, Cations, Divalent, Magnesium, Magnetic Resonance Spectroscopy, Protein Binding, Protein Conformation, Thermus thermophilus, Antiporters
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