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

Abstract
Data availability
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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

(2021) Structure of apo-EleNRMT in complex with two nanobodies at 3.5A
PDB 7QIA.

https://doi.org/10.2210/pdb7QIA/pdb
(2021) cryo-EM map of apo-EleNRMT in complex with two nanobodies at 3.5A
EMDB 13985.

https://www.emdataresource.org/EMD-13985
(2021) Structure of magnesium-bound EleNRMT in complex with two nanobodies at 4.1A
PDB 7QIC.

https://doi.org/10.2210/pdb7QIC/pdb
(2021) cryo-EM map of magnesium-bound EleNRMT in complex with two nanobodies at 4.1A
EMDB 13987.

https://www.emdataresource.org/EMD-13987
(2022) X-Ray Structure of apo-EleNRMT in complex with two Nanobodies at 4.1A
PDB 7QJI.

https://www.rcsb.org/structure/unreleased/7QJI
(2022) X-Ray Structure of a Mn2+ soak of EleNRMT in complex with two Nanobodies at 4.6A
PDB 7QJJ.

https://www.rcsb.org/structure/unreleased/7QJJ

Article and author information

Author details

Karthik Ramanadane

Department of Biochemistry, University of Zurich, Zürich, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7188-0250
Monique S Straub

Department of Biochemistry, University of Zurich, Zürich, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7721-5048
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.

"This ORCID iD identifies the author of this article:" 0000-0002-2193-6129
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.

"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.

Copyright

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.