Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

Abstract

Members of the ubiquitous SLC11/NRAMP family catalyze the uptake of divalent transition metal ions into cells. They have evolved to efficiently select these trace elements from a large pool of Ca2+ and Mg2+, which are both orders of magnitude more abundant, and to concentrate them in the cytoplasm aided by the cotransport of H+ serving as energy source. In the present study, we have characterized a member of a distant clade of the family found in prokaryotes, termed NRMTs, that were proposed to function as transporters of Mg2+. The protein transports Mg2+ and Mn2+ but not Ca2+ by a mechanism that is not coupled to H+. Structures determined by cryo-EM and X-ray crystallography revealed a generally similar protein architecture compared to classical NRAMPs, with a restructured ion binding site whose increased volume provides suitable interactions with ions that likely have retained much of their hydration shell.

Data availability

The cryo-EM density maps of the EleNRM-Nb complex in absence and presence of Mg2+ have been deposited in the Electron Microscopy Data Bank under ID codes EMD-13985 and EMD-13987, respectively. The coordinates for the atomic model of the EleNRM-Nb complex in absence of Mg2+ refined against the 3.4 Å cryo-EM density and the coordinates of the EleNRMTts-Nb1,2 complex in presence of Mg2+ refined against the 4.1 Å cryo-EM density have been deposited in the Protein Data Bank under ID codes 7QIA and 7QIC. The coordinates and structure factors of the EleNRMTts-Nb1,2 complexes in Mg2+ and Mn2+ have been deposited in the Protein Data Bank with the accession codes 7QJI and 7QJJ. All datasets will be accessible upon publication. Source data files have been provided for Figures 1, Figure 1-figure supplement 1, Figure 2, Figure 2-figure supplement 1, Figure 3, Figure 2-figure supplement 2, Figure 4, Figure 4-figure supplement 1, Figure 8.

The following data sets were generated

Article and author information

Author details

  1. Karthik Ramanadane

    Department of Biochemistry, University of Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7188-0250
  2. Monique S Straub

    Department of Biochemistry, University of Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7721-5048
  3. Raimund Dutzler

    Department of Biochemistry, University of Zurich, Zürich, Switzerland
    For correspondence
    dutzler@bioc.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2193-6129
  4. Cristina Manatschal

    Department of Biochemistry, University of Zurich, Zürich, Switzerland
    For correspondence
    c.manatschal@bioc.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4907-7303

Funding

Swiss National Science Foundation (NCCR TransCure)

  • Raimund Dutzler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Randy B Stockbridge, University of Michigan, United States

Version history

  1. Received: October 9, 2021
  2. Preprint posted: October 19, 2021 (view preprint)
  3. Accepted: December 17, 2021
  4. Accepted Manuscript published: January 10, 2022 (version 1)
  5. Version of Record published: February 1, 2022 (version 2)

Copyright

© 2022, Ramanadane et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Karthik Ramanadane
  2. Monique S Straub
  3. Raimund Dutzler
  4. Cristina Manatschal
(2022)
Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family
eLife 11:e74589.
https://doi.org/10.7554/eLife.74589

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https://doi.org/10.7554/eLife.74589

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