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Nat Commun. 2015 Oct 13;6:8545. doi: 10.1038/ncomms9545.

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

Author information

1
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
2
Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
3
Structural Biology Program, Centenary Institute, Locked Bag 6, Sydney, New South Wales 2042, Australia.
4
Faculty of Medicine, Central Clinical School, University of Sydney, Sydney, New South Wales 2006, Australia.
5
Technical office, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
6
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8562, Japan.

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.

PMID:
26461048
PMCID:
PMC4633820
DOI:
10.1038/ncomms9545
[Indexed for MEDLINE]
Free PMC Article

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