Mechanism of Ca transport by ferroportin.

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