Abstract

Ferroportin (Fpn) is a transporter that releases ferrous ion (Fe2+) from cells and is important for homeostasis of iron in circulation. Export of one Fe2+ by Fpn is coupled to import of two H+ to maintain charge balance. Here we show that human Fpn (HsFpn) binds to and mediates Ca2+ transport. We determine the structure of Ca2+-bound HsFpn and identify a single Ca2+ binding site distinct from the Fe2+ binding sites. Further studies validate the Ca2+ binding site and show that Ca2+ transport is not coupled to transport of another ion. In addition, Ca2+ transport is significantly inhibited in the presence of Fe2+ but not vice versa. Function of Fpn as a Ca2+ uniporter may allow regulation of iron homeostasis by Ca2+.

Data availability

The cryo-EM density map of nanodisc-encircled HsFpn-11F9 in the presence Ca2+ has been deposited in the Electron Microscopy Data Bank (https://www.ebi.ac.uk/pdbe/emdb/) under accession code EMD-27497. The corresponding atomic coordinate file has been deposited in the Protein Data Bank (http://www.rcsb.org) under ID code 8DL6. Uncropped gel and blot images are available as source files.

The following data sets were generated

Article and author information

Author details

  1. Jiemin Shen

    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3977-0681
  2. Azaan Saalim Wilbon

    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ming Zhou

    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States
    For correspondence
    mzhou@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
  4. Yaping Pan

    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States
    For correspondence
    yaping.pan@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7459-4217

Funding

National Institutes of Health (HL157473)

  • Yaping Pan

National Institutes of Health (DK122784)

  • Ming Zhou

National Institutes of Health (HL086392)

  • Ming Zhou

National Institutes of Health (GM145416)

  • Ming Zhou

Cancer Prevention and Research Institute of Texas (R1223)

  • Ming Zhou

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

Reviewing Editor

  1. David Drew, Stockholm University, Sweden

Version history

  1. Preprint posted: August 24, 2022 (view preprint)
  2. Received: August 24, 2022
  3. Accepted: January 16, 2023
  4. Accepted Manuscript published: January 17, 2023 (version 1)
  5. Version of Record published: January 27, 2023 (version 2)

Copyright

© 2023, Shen 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. Jiemin Shen
  2. Azaan Saalim Wilbon
  3. Ming Zhou
  4. Yaping Pan
(2023)
Mechanism of Ca2+ transport by ferroportin
eLife 12:e82947.
https://doi.org/10.7554/eLife.82947

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https://doi.org/10.7554/eLife.82947

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