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+ .