8dl6 | pdb_00008dl6
Cryo-EM structure of human ferroportin/slc40 bound to Ca2+ in nanodisc
Structural highlights
DiseaseS40A1_HUMAN Hemochromatosis type 4. The disease is caused by variants affecting the gene represented in this entry. FunctionS40A1_HUMAN Major iron transporter that plays a key role in balancing cellular and systemic iron levels (PubMed:29237594, PubMed:22682227, PubMed:15692071). Transports iron from intestinal, splenic, and hepatic cells into the blood to provide iron to other tissues (By similarity). Controls therefore dietary iron uptake, iron recycling by macrophages, and release of iron stores in hepatocytes (By similarity). When iron is in excess, hepcidin/HAMP levels increase resulting in a degradation of ferroportin/SLC40A1 limiting the iron efflux to plasma (PubMed:22682227, PubMed:29237594, PubMed:32814342).[UniProtKB:Q9JHI9][1] [2] [3] [4] Publication Abstract from PubMedFerroportin (Fpn) is a transporter that releases ferrous ion (Fe(2+)) from cells and is important for homeostasis of iron in circulation. Export of one Fe(2+) by Fpn is coupled to import of two H(+) to maintain charge balance. Here we show that human Fpn (HsFpn) binds to and mediates Ca(2+) transport. We determine the structure of Ca(2+)-bound HsFpn and identify a single Ca(2+) binding site distinct from the Fe(2+) binding sites. Further studies validate the Ca(2+) binding site and show that Ca(2+) transport is not coupled to transport of another ion. In addition, Ca(2+) transport is significantly inhibited in the presence of Fe(2+) but not vice versa. Function of Fpn as a Ca(2+) uniporter may allow regulation of iron homeostasis by Ca(2+). Mechanism of Ca(2+) transport by ferroportin.,Shen J, Wilbon AS, Zhou M, Pan Y Elife. 2023 Jan 17;12:e82947. doi: 10.7554/eLife.82947. PMID:36648329[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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