Mechanism of Ca2+ Transport by Ferroportin

Authors

Jiemin Shen
Azaan Saalim Wilbon
Ming Zhou
Yaping Pan

Publication Date

1-17-2023

Journal

eLife

DOI

10.7554/eLife.82947

PMID

36648329

PMCID

PMC9883014

PubMedCentral® Posted Date

1-17-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Binding Sites, Cation Transport Proteins, Homeostasis, Iron, Calcium

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+.

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