5AYO

Crystal structure of a bacterial homologue of iron transporter ferroportin in inward-facing state

Summary for 5AYO

• Entry DOI: 10.2210/pdb5ayo/pdb
• Related: 5AYM 5AYN
• Descriptor: Solute carrier family 39 (Iron-regulated transporter), POTASSIUM ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: alpha helical, transport protein
• Biological source: Bdellovibrio bacteriovorus
• Total number of polymer chains: 1
• Total formula weight: 49127.24

Authors

Taniguchi, R.,Kato, H.E.,Font, J.,Deshpande, C.N.,Ishitani, R.,Jormakka, M.,Nureki, O. (deposition date: 2015-08-25, release date: 2015-11-04, Last modification date: 2024-03-20)

Primary citation

Taniguchi, R.,Kato, H.E.,Font, J.,Deshpande, C.N.,Wada, M.,Ito, K.,Ishitani, R.,Jormakka, M.,Nureki, O.
Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin
Nat Commun, 6:8545-8545, 2015

PubMed 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.

PubMed: 26461048
DOI: 10.1038/ncomms9545

Experimental method

X-RAY DIFFRACTION (3.3 Å)