ATP-dependent modulation of MgtE in Mg2+ homeostasis

Atsuhiro Tomita, Mingfeng Zhang, Fei Jin, Wenhui Zhuang, Hironori Takeda, Tatsuro Maruyama, Masanori Osawa, Ken Ichi Hashimoto, Hisashi Kawasaki, Koichi Ito, Naoshi Dohmae, Ryuichiro Ishitani, Ichio Shimada, Zhiqiang Yan, Motoyuki Hattori, Osamu Nureki

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16 Citations (Scopus)

Abstract

Magnesium is an essential ion for numerous physiological processes. MgtE is a Mg2+ selective channel involved in the maintenance of intracellular Mg2+ homeostasis, whose gating is regulated by intracellular Mg2+ levels. Here, we report that ATP binds to MgtE, regulating its Mg2+-dependent gating. Crystal structures of MgtE-ATP complex show that ATP binds to the intracellular CBS domain of MgtE. Functional studies support that ATP binding to MgtE enhances the intracellular domain affinity for Mg2+ within physiological concentrations of this divalent cation, enabling MgtE to function as an in vivo Mg2+ sensor. ATP dissociation from MgtE upregulates Mg2+ influx at both high and low intracellular Mg2+ concentrations. Using site-directed mutagenesis and structure based-electrophysiological and biochemical analyses, we identify key residues and main structural changes involved in the process. This work provides the molecular basis of ATP-dependent modulation of MgtE in Mg2+ homeostasis.

Original languageEnglish
Article number148
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Tomita, A., Zhang, M., Jin, F., Zhuang, W., Takeda, H., Maruyama, T., Osawa, M., Hashimoto, K. I., Kawasaki, H., Ito, K., Dohmae, N., Ishitani, R., Shimada, I., Yan, Z., Hattori, M., & Nureki, O. (2017). ATP-dependent modulation of MgtE in Mg2+ homeostasis. Nature communications, 8(1), [148]. https://doi.org/10.1038/s41467-017-00082-w