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Crystal structure of the MgtE Mg2+ transporter

Nature volume 448, pages 1072–1075 (2007)Cite this article

Abstract

The magnesium ion Mg2+ is a vital element involved in numerous physiological processes. Mg2+ has the largest hydrated radius among all cations, whereas its ionic radius is the smallest. It remains obscure how Mg2+ transporters selectively recognize and dehydrate the large, fully hydrated Mg2+ cation for transport1. Recently the crystal structures of the CorA Mg2+ transporter2,3,4,5 were reported6,7,8. The MgtE family of Mg2+ transporters is ubiquitously distributed in all phylogenetic domains9,10,11, and human homologues have been functionally characterized and suggested to be involved in magnesium homeostasis12,13,14. However, the MgtE transporters have not been thoroughly characterized. Here we determine the crystal structures of the full-length Thermus thermophilus MgtE at 3.5 Å resolution, and of the cytosolic domain in the presence and absence of Mg2+ at 2.3 Å and 3.9 Å resolutions, respectively. The transporter adopts a homodimeric architecture, consisting of the carboxy-terminal five transmembrane domains and the amino-terminal cytosolic domains, which are composed of the superhelical N domain and tandemly repeated cystathionine-β-synthase domains. A solvent-accessible pore nearly traverses the transmembrane domains, with one potential Mg2+ bound to the conserved Asp 432 within the pore. The transmembrane (TM)5 helices from both subunits close the pore through interactions with the ‘connecting helices’, which connect the cystathionine-β-synthase and transmembrane domains. Four putative Mg2+ ions are bound at the interface between the connecting helices and the other domains, and this may lock the closed conformation of the pore. A structural comparison of the two states of the cytosolic domains showed the Mg2+-dependent movement of the connecting helices, which might reorganize the transmembrane helices to open the pore. These findings suggest a homeostasis mechanism, in which Mg2+ bound between cytosolic domains regulates Mg2+ flux by sensing the intracellular Mg2+ concentration. Whether this presumed regulation controls gating of an ion channel or opening of a secondary active transporter remains to be determined.

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Figure 1: Structure of the MgtE Mg 2+ transporter.
Figure 2: MgtE pore.
Figure 3: Putative Mg 2+ binding sites.
Figure 4: Proposed Mg 2+ homeostasis mechanism.

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Acknowledgements

We thank the beam-line staffs at BL41XU of SPring-8 and BL5A of KEK for technical help during data collection, and Y. Sugita and T. Tsukazaki for suggestions. This work was supported by a SORST Program grant from JST (Japan Science and Technology) to O.N., by grants from MEXT to R.I., S.F. and O.N., and by grants from the Society for Research on Umami Taste, the Danone Institute, and the Yamazaki Foundation to O.N.

Author Contributions M.H. designed the research, carried out the crystallization of the full-length MgtE and the structure determinations, and wrote the paper, with editing from S.F., R.I. and O.N. Y.T. carried out the crystallization of the cytosolic domain of MgtE. S.F., R.I. and O.N. assisted with the structural determination. All authors discussed the results and commented on the manuscript. O.N. supervised the work.

The coordinates and structure factors have been deposited in the Protein Data Bank, under the accession codes 2YVX, 2YVY and 2YVZ for the full-length MgtE, and the Mg2+-bound and Mg2+-free cytosolic domains of MgtE, respectively.

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Authors and Affiliations

  1. Department of Biological Information, Graduate School of Bioscience and Biotechnology,

    Motoyuki Hattori, Yoshiki Tanaka, Ryuichiro Ishitani & Osamu Nureki

  2. Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan,

    Shuya Fukai

  3. SORST, JST, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan,

    Osamu Nureki

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  1. Motoyuki Hattori
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Correspondence to Osamu Nureki.

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This file contains Supplementary Discussion, Supplementary Figures S1-S12 with Legends, Supplementary Tables S1-S3 and additional references. (PDF 17697 kb)

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Hattori, M., Tanaka, Y., Fukai, S. et al. Crystal structure of the MgtE Mg2+ transporter. Nature 448, 1072–1075 (2007). https://doi.org/10.1038/nature06093

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