Mg2+‐dependent gating of bacterial MgtE channel underlies Mg2+ homeostasis |
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| Authors: | Yoshiki Tanaka Tomoya Tsukazaki Ryuichiro Ishitani Michael E Maguire Koichi Ito Andres Maturana Osamu Nureki |
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| Institution: | 1. Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, Minato‐ku, Tokyo, Japan;2. Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA;3. Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Minato‐ku, Tokyo, Japan;4. Global Edge Institute, Tokyo Institute of Technology, E31, Tokyo, Japan;5. Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori‐ku, Yokohama‐shi, Kanagawa, Japan |
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| Abstract: | The MgtE family of Mg2+ 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 Mg2+ suggested a Mg2+‐homeostasis mechanism, in which the MgtE cytosolic domain acts as a ‘Mg2+ sensor’ to regulate the gating of the ion‐conducting pore in response to the intracellular Mg2+ 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 Mg2+‐selective channel gated by Mg2+ and elucidated the Mg2+‐dependent gating mechanism of MgtE, using X‐ray crystallographic, genetic, biochemical, and electrophysiological analyses. These structural and functional results have clarified the control of Mg2+ homeostasis through cooperative Mg2+ binding to the MgtE cytosolic domain. |
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| Keywords: | electrophysiology gating mechanism ion channel structural biology |
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