Mg2+-dependent gating of bacterial MgtE channel underlies Mg2+ homeostasis

The MgtE family of Mg 2+ transporters is ubiquitously distributed in all phylogenetic domains. Recent crystal structures of the full‐length MgtE and of its cytosolic domain in the presence and absence of Mg 2+ suggested a Mg 2+ ‐homeostasis mechanism, in which the MgtE cytosolic domain acts as a ‘Mg 2+ sensor’ to regulate the gating of the ion‐conducting pore in response to the intracellular Mg 2+ concentration. However, complementary functional analyses to confirm the proposed model have been lacking. Moreover, the limited resolution of the full‐length structure precluded an unambiguous characterization of these regulatory divalent‐cation‐binding sites. Here, we showed that MgtE is a highly Mg 2+ ‐selective channel gated by Mg 2+ and elucidated the Mg 2+ ‐dependent gating mechanism of MgtE, using X‐ray crystallographic, genetic, biochemical, and electrophysiological analyses. These structural and functional results have clarified the control of Mg 2+ homeostasis through cooperative Mg 2+ binding to the MgtE cytosolic domain.