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

Author

Listed:
  • Reiya Taniguchi

    (Graduate School of Science, The University of Tokyo
    Global Research Cluster, RIKEN)

  • Hideaki E. Kato

    (Graduate School of Science, The University of Tokyo
    Global Research Cluster, RIKEN
    Present address: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.)

  • Josep Font

    (Structural Biology Program, Centenary Institute
    Faculty of Medicine, Central Clinical School, University of Sydney)

  • Chandrika N. Deshpande

    (Structural Biology Program, Centenary Institute
    Faculty of Medicine, Central Clinical School, University of Sydney)

  • 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
    Global Research Cluster, RIKEN)

  • Mika Jormakka

    (Structural Biology Program, Centenary Institute
    Faculty of Medicine, Central Clinical School, University of Sydney)

  • Osamu Nureki

    (Graduate School of Science, The University of Tokyo
    Global Research Cluster, RIKEN)

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.

Suggested Citation

  • Reiya Taniguchi & Hideaki E. Kato & Josep Font & Chandrika N. Deshpande & Miki Wada & Koichi Ito & Ryuichiro Ishitani & Mika Jormakka & Osamu Nureki, 2015. "Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9545
    DOI: 10.1038/ncomms9545
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    Cited by:

    1. Dohyun Im & Mika Jormakka & Narinobu Juge & Jun-ichi Kishikawa & Takayuki Kato & Yukihiko Sugita & Takeshi Noda & Tomoko Uemura & Yuki Shiimura & Takaaki Miyaji & Hidetsugu Asada & So Iwata, 2024. "Neurotransmitter recognition by human vesicular monoamine transporter 2," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Lei Wang & Jiangguo Zhang & Dali Wang & Chen Song, 2022. "Membrane contact probability: An essential and predictive character for the structural and functional studies of membrane proteins," PLOS Computational Biology, Public Library of Science, vol. 18(3), pages 1-27, March.

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