Mechanism of Ca2+ transport by ferroportin

Abstract
Data availability
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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

1. Shen J
2. Wilbon AS
3. Pan Y
4. Zhou M
(2023) Cryo-EM structure of human ferroportin/slc40 bound to Ca2+ in nanodisc
PBD, 8DL6.

https://www.rcsb.org/structure/8DL6
1. Pan Y
2. Shen J
3. Wilbon AS
4. Zhou M
(2023) Cryo-EM structure of human ferroportin/slc40 bound to Ca2+ in nanodisc
EMD-27497.

https://www.ebi.ac.uk/emdb/EMD-27497

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-3977-0681
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.
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.
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.

"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.

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.