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== Publication Abstract from PubMed ==

Magnesium ions (Mg(2+)) play an essential role in cellular physiology. In mitochondria, protein and ATP synthesis and various metabolic pathways are directly regulated by Mg(2+). MRS2, a magnesium channel located in the inner mitochondrial membrane, mediates the influx of Mg(2+) into the mitochondrial matrix and regulates Mg(2+) homeostasis. Knockdown of MRS2 in human cells leads to reduced uptake of Mg(2+) into mitochondria and disruption of the mitochondrial metabolism. Despite the importance of MRS2, the Mg(2+) translocation and regulation mechanisms of MRS2 are still unclear. Here, using cryo-EM we determined the structure of human MRS2 in the presence and absence of Mg(2+) at 2.8 A and 3.3 A, respectively. From the homo-pentameric structures, we identified R332 and M336 as major gating residues, which were then tested using mutagenesis and two cellular divalent ion uptake assays. A network of hydrogen bonds was found connecting the gating residue R332 to the soluble domain, potentially regulating the gate. Two Mg(2+)-binding sites were identified in the MRS2 soluble domain, distinct from the two sites previously reported in CorA, a homolog of MRS2 in prokaryotes. Altogether, this study provides the molecular basis for understanding the Mg(2+) translocation and regulatory mechanisms of MRS2.

Cryo-EM structures of human magnesium channel MRS2 reveal gating and regulatory mechanisms.,Lai LTF, Balaraman J, Zhou F, Matthies D bioRxiv. 2023 Aug 23:2023.08.22.553867. doi: 10.1101/2023.08.22.553867. Preprint. PMID:37662257<ref>PMID:37662257</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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