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bioRxiv · 10.1101/2022.08.23.504983

Mechanism of Ca2+ transport by ferroportin

Shen, J.·Wilbon, A. S.·Pan, Y.·Zhou, M.
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Abstract

Ferroportin (Fpn) is a transporter that releases Fe2+ from cells and is important for iron homeostasis in circulation. Export of Fe2+ by Fpn is coupled to import of H+ to maintain charge balance. Although Ca2+ was shown to modulate Fe2+ transport in Fpn, transport of Ca2+ by Fpn has not been demonstrated. Here we show that human Fpn (HsFpn) mediates Ca2+ transport, and that the Ca2+ transport does not rely on the transport of other ions. 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 inhibited in the presence of Fe2+ but not vice versa. Function of Fpn as a Ca2+ uniporter in the absence of Fe2+ provides a molecular basis for regulations of iron homeostasis by Ca2+.

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Shen, J., Wilbon, A. S., Pan, Y., Zhou, M.. 2022-08-24. Mechanism of Ca2+ transport by ferroportin. https://doi.org/10.1101/2022.08.23.504983

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