Mechanism of Ca(2+) transport by ferroportin

Ferroportin (Fpn) is a transporter that releases ferrous ion (Fe(2+)) from cells and is important for homeostasis of iron in circulation. Export of one Fe(2+) by Fpn is coupled to import of two H(+) to maintain charge balance. Here, we show that human Fpn (HsFpn) binds to and mediates Ca(2+) transport. We determine the structure of Ca(2+)-bound HsFpn and identify a single Ca(2+) binding site distinct from the Fe(2+) binding sites. Further studies validate the Ca(2+) binding site and show that Ca(2+) transport is not coupled to transport of another ion. In addition, Ca(2+) transport is significantly inhibited in the presence of Fe(2+) but not vice versa. Function of Fpn as a Ca(2+) uniporter may allow regulation of iron homeostasis by Ca(2+).