ArticleThe Biochemical journal2014
Nucleotide binding triggers a conformational change of the CBS module of the magnesium transporter CNNM2 from a twisted towards a flat structure.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- Two novel variants inFrontiers in genetics · 2025Article
- Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 2024Article
- Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.eLife · 2023Article
- Structural insights into regulation of TRPM7 divalent cation uptake by the small GTPase ARL15.bioRxiv : the preprint server for biology · 2023Article
- Structural and functional comparison of magnesium transporters throughout evolution.Cellular and molecular life sciences : CMLS · 2022Review
- The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone.International journal of molecular sciences · 2022Article
- Association between host genetics of sheep and the rumen microbial composition.Tropical animal health and production · 2022Article
- NovelFrontiers in genetics · 2022Article
- CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.PLoS biology · 2021Article
- Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome.Nutrients · 2021Article
- Diseases caused by mutations in the NaAmerican journal of physiology. Cell physiology · 2021Review
- Crystal structure of an archaeal CorB magnesium transporter.Nature communications · 2021Article
- Article
- Structural basis for the MgScience advances · 2021Article
- Article
- Case Report: CNNM2 Mutations Cause Damaged Brain Development and Intractable Epilepsy in a Patient Without Hypomagnesemia.Frontiers in genetics · 2021Article
- Structural Insights into the Intracellular Region of the Human Magnesium Transport Mediator CNNM4.International journal of molecular sciences · 2019Article
- Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators.International journal of molecular sciences · 2019Review
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Recent studies suggest CNNM2 (cyclin M2) to be part of the long-sought basolateral Mg2+ extruder at the renal distal convoluted tubule, or its regulator. In the present study, we explore structural features and ligand-binding capacities of the Bateman module of CNNM2 (residues 429-584), an intracellular domain structurally equivalent to the region involved in Mg2+ handling by the bacterial Mg2+ transporter MgtE, and AMP binding by the Mg2+ efflux protein CorC. Additionally, we studied the structural impact of the pathogenic mutation T568I located in this region. Our crystal structures reveal that nucleotides such as AMP, ADP or ATP bind at only one of the two cavities present in CNNM2429-584. Mg2+ favours ATP binding by alleviating the otherwise negative charge repulsion existing between acidic residues and the polyphosphate group of ATP. In crystals CNNM2429-584 forms parallel dimers, commonly referred to as CBS (cystathionine β-synthase) modules. Interestingly, nucleotide binding triggers a conformational change in the CBS module from a twisted towards a flat disc-like structure that mostly affects the structural elements connecting the Bateman module with the transmembrane region. We furthermore show that the T568I mutation, which causes dominant hypomagnesaemia, mimics the structural effect induced by nucleotide binding. The results of the present study suggest that the T568I mutation exerts its pathogenic effect in humans by constraining the conformational equilibrium of the CBS module of CNNM2, which becomes 'locked' in its flat form.
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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.