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

Autor:	Taniguchi R; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.; Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan., Kato HE; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.; Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan., Font J; Structural Biology Program, Centenary Institute, Locked Bag 6, Sydney, New South Wales 2042, Australia.; Faculty of Medicine, Central Clinical School, University of Sydney, Sydney, New South Wales 2006, Australia., Deshpande CN; Structural Biology Program, Centenary Institute, Locked Bag 6, Sydney, New South Wales 2042, Australia.; Faculty of Medicine, Central Clinical School, University of Sydney, Sydney, New South Wales 2006, Australia., Wada M; Technical office, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan., Ito K; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8562, Japan., Ishitani R; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.; Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan., Jormakka M; Structural Biology Program, Centenary Institute, Locked Bag 6, Sydney, New South Wales 2042, Australia.; Faculty of Medicine, Central Clinical School, University of Sydney, Sydney, New South Wales 2006, Australia., Nureki O; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.; Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2015 Oct 13; Vol. 6, pp. 8545. Date of Electronic Publication: 2015 Oct 13.
DOI:	10.1038/ncomms9545
Abstrakt:	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.
Databáze:	MEDLINE
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