IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9545.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9545
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9545?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9545. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.