5ayo

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

Structural highlights

5ayo is a 1 chain structure with sequence from Bdellovibrio bacteriovorus HD100. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FPN_BDEBA Iron transpoter that exports Fe(2+) from the cell. Also binds to Co(2+) and Ni(2+). May act as a multivalent divalent metal transporter (PubMed:26608034). The transporter is composed of 12 transmembrane (TM) helices organized into N-terminal (TM1-6) and C-terminal (TM7-12) domains. The substrate-binding site is formed at the interface of the two domains and is alternately accessible from either side of the membrane. The transport cycle is viewed as a series of ligand-induced conformational changes that include open outward and open inward states (PubMed:26461048, PubMed:30082682).^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin.,Taniguchi R, Kato HE, Font J, Deshpande CN, Wada M, Ito K, Ishitani R, Jormakka M, Nureki O Nat Commun. 2015 Oct 13;6:8545. doi: 10.1038/ncomms9545. PMID:26461048^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Taniguchi R, Kato HE, Font J, Deshpande CN, 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. 2015 Oct 13;6:8545. doi: 10.1038/ncomms9545. PMID:26461048 doi:http://dx.doi.org/10.1038/ncomms9545
↑ Bonaccorsi di Patti MC, Polticelli F, Tortosa V, Furbetta PA, Musci G. A bacterial homologue of the human iron exporter ferroportin. FEBS Lett. 2015 Dec 21;589(24 Pt B):3829-35. PMID:26608034 doi:10.1016/j.febslet.2015.11.025
↑ Deshpande CN, Ruwe TA, Shawki A, Xin V, Vieth KR, Valore EV, Qiao B, Ganz T, Nemeth E, Mackenzie B, Jormakka M. Calcium is an essential cofactor for metal efflux by the ferroportin transporter family. Nat Commun. 2018 Aug 6;9(1):3075. doi: 10.1038/s41467-018-05446-4. PMID:30082682 doi:http://dx.doi.org/10.1038/s41467-018-05446-4
↑ Taniguchi R, Kato HE, Font J, Deshpande CN, 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. 2015 Oct 13;6:8545. doi: 10.1038/ncomms9545. PMID:26461048 doi:http://dx.doi.org/10.1038/ncomms9545

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OCA

[1] Taniguchi R, Kato HE, Font J, Deshpande CN, 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. 2015 Oct 13;6:8545. doi: 10.1038/ncomms9545. PMID:26461048 doi:http://dx.doi.org/10.1038/ncomms9545

[2] Bonaccorsi di Patti MC, Polticelli F, Tortosa V, Furbetta PA, Musci G. A bacterial homologue of the human iron exporter ferroportin. FEBS Lett. 2015 Dec 21;589(24 Pt B):3829-35. PMID:26608034 doi:10.1016/j.febslet.2015.11.025

[3] Deshpande CN, Ruwe TA, Shawki A, Xin V, Vieth KR, Valore EV, Qiao B, Ganz T, Nemeth E, Mackenzie B, Jormakka M. Calcium is an essential cofactor for metal efflux by the ferroportin transporter family. Nat Commun. 2018 Aug 6;9(1):3075. doi: 10.1038/s41467-018-05446-4. PMID:30082682 doi:http://dx.doi.org/10.1038/s41467-018-05446-4

[4] Taniguchi R, Kato HE, Font J, Deshpande CN, 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. 2015 Oct 13;6:8545. doi: 10.1038/ncomms9545. PMID:26461048 doi:http://dx.doi.org/10.1038/ncomms9545

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5ayo

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

Structural highlights

Function

Publication Abstract from PubMed

References

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5ayo

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

Structural highlights

Function

Publication Abstract from PubMed

References

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