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

Reiya Taniguchi, Hideaki E. Kato, Josep Font, Chandrika N. Deshpande, Miki Wada, Koichi Ito, Ryuichiro Ishitani (), Mika Jormakka () and Osamu Nureki ()
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Reiya Taniguchi: Graduate School of Science, The University of Tokyo
Hideaki E. Kato: Graduate School of Science, The University of Tokyo
Josep Font: Structural Biology Program, Centenary Institute
Chandrika N. Deshpande: Structural Biology Program, Centenary Institute
Miki Wada: Technical office, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai
Koichi Ito: Graduate School of Frontier Sciences, The University of Tokyo
Ryuichiro Ishitani: Graduate School of Science, The University of Tokyo
Mika Jormakka: Structural Biology Program, Centenary Institute
Osamu Nureki: Graduate School of Science, The University of Tokyo

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract In vertebrates, the iron exporter ferroportin releases Fe2+ 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.

Date: 2015
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DOI: 10.1038/ncomms9545

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