Structural basis for the Mg 2+ recognition and regulation of the CorC Mg 2+ transporter
Open Access
- 12 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (7), eabe6140
- https://doi.org/10.1126/sciadv.abe6140
Abstract
The CNNM/CorC family proteins are Mg2+ transporters that are widely distributed in all domains of life. In bacteria, CorC has been implicated in the survival of pathogenic microorganisms. In humans, CNNM proteins are involved in various biological events, such as body absorption/reabsorption of Mg2+ and genetic disorders. Here, we determined the crystal structure of the Mg2+-bound CorC TM domain dimer. Each protomer has a single Mg2+ binding site with a fully dehydrated Mg2+ ion. The residues at the Mg2+ binding site are strictly conserved in both human CNNM2 and CNNM4, and many of these residues are associated with genetic diseases. Furthermore, we determined the structures of the CorC cytoplasmic region containing its regulatory ATP-binding domain. A combination of structural and functional analyses not only revealed the potential interface between the TM and cytoplasmic domains but also showed that ATP binding is important for the Mg2+ export activity of CorC.Funding Information
- Japan Society for the Promotion of Science
- Japan Society for the Promotion of Science
- Ministry of Science and Technology of the People’s Republic of China
This publication has 68 references indexed in Scilit:
- Basolateral Mg2+ Extrusion via CNNM4 Mediates Transcellular Mg2+ Transport across Epithelia: A Mouse ModelPLoS Genetics, 2013
- Structural insights into the mechanisms of Mg 2+ uptake, transport, and gating by CorAProceedings of the National Academy of Sciences of the United States of America, 2012
- Membrane Topology and Intracellular Processing of Cyclin M2 (CNNM2)Online Journal of Public Health Informatics, 2012
- Cellular magnesium homeostasisArchives of Biochemistry and Biophysics, 2011
- CNNM2, Encoding a Basolateral Protein Required for Renal Mg2+ Handling, Is Mutated in Dominant HypomagnesemiaAmerican Journal of Human Genetics, 2011
- Mg2+-dependent gating of bacterial MgtE channel underlies Mg2+ homeostasisThe EMBO Journal, 2009
- Crystallizing membrane proteins using lipidic mesophasesNature Protocols, 2009
- Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis ImperfectaAmerican Journal of Human Genetics, 2009
- Mutations in CNNM4 Cause Recessive Cone-Rod Dystrophy with Amelogenesis ImperfectaAmerican Journal of Human Genetics, 2009
- Phasercrystallographic softwareJournal of Applied Crystallography, 2007