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  • Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin.

Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin.

Nature communications (2015-10-16)
Reiya Taniguchi, Hideaki E Kato, Josep Font, Chandrika N Deshpande, Miki Wada, Koichi Ito, Ryuichiro Ishitani, Mika Jormakka, Osamu Nureki
ABSTRACT

In vertebrates, the iron exporter ferroportin releases Fe(2+) from cells into plasma, thereby maintaining iron homeostasis. The transport activity of ferroportin is suppressed by the peptide hormone hepcidin, which exhibits upregulated expression in chronic inflammation, causing iron-restrictive anaemia. However, due to the lack of structural information about ferroportin, the mechanisms of its iron transport and hepcidin-mediated regulation remain largely elusive. Here we report the crystal structures of a putative bacterial homologue of ferroportin, BbFPN, in both the outward- and inward-facing states. Despite undetectable sequence similarity, BbFPN adopts the major facilitator superfamily fold. A comparison of the two structures reveals that BbFPN undergoes an intra-domain conformational rearrangement during the transport cycle. We identify a substrate metal-binding site, based on structural and mutational analyses. Furthermore, the BbFPN structures suggest that a predicted hepcidin-binding site of ferroportin is located within its central cavity. Thus, BbFPN may be a valuable structural model for iron homeostasis regulation by ferroportin.

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