Calcium is an essential cofactor for metal efflux by the ferroportin transporter family

Calcium is an essential cofactor for metal efflux by the ferroportin transporter family.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41467-018-05446-4
Journal or Publication Title: Nature Communications
Volume: 9
Number: 1
Date: 2018
Divisions: Structural Biology
Depositing User: General Admin
Identification Number: 10.1038/s41467-018-05446-4
ISSN: 2041-1723
Date Deposited: 03 Jan 2021 22:47
Abstract:

Ferroportin (Fpn)-the only known cellular iron exporter-transports dietary and recycled iron into the blood plasma, and transfers iron across the placenta. Despite its central role in iron metabolism, our molecular understanding of Fpn-mediated iron efflux remains incomplete. Here, we report that Ca2+ is required for human Fpn transport activity. Whereas iron efflux is stimulated by extracellular Ca2+ in the physiological range, Ca2+ is not transported. We determine the crystal structure of a Ca2+-bound BbFpn, a prokaryotic orthologue, and find that Ca2+ is a cofactor that facilitates a conformational change critical to the transport cycle. We also identify a substrate pocket accommodating a divalent transition metal complexed with a chelator. These findings support a model of iron export by Fpn and suggest a link between plasma calcium and iron homeostasis.

Creators:
Creators
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Deshpande, Chandrika N.
UNSPECIFIED
Ruwe, T. Alex
UNSPECIFIED
Shawki, Ali
UNSPECIFIED
Xin, Vicky
UNSPECIFIED
Vieth, Kyle R.
UNSPECIFIED
Valore, Erika V.
UNSPECIFIED
Qiao, Bo
UNSPECIFIED
Ganz, Tomas
UNSPECIFIED
Nemeth, Elizabeta
UNSPECIFIED
Mackenzie, Bryan
UNSPECIFIED
Jormakka, Mika
UNSPECIFIED
Last Modified: 03 Jan 2021 22:47
URI: https://eprints.centenary.org.au/id/eprint/523

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