A structural model of human ferroportin and of its iron binding site.

Abstract

A structural model of human ferroportin has been built using two Escherichia coli proteins belonging to the major facilitator superfamily of transporters. A potential iron binding site was identified in the inward-open conformation of the model, and its relevance was tested through measurement of iron export of HEK293T cells expressing wild-type or mutated ferroportin. Aspartates 39 and 181 were found to be essential for the transport ability of the protein. Noteworthy, the D181V mutation is naturally found in type 4 hemochromatosis with reticuloendothelial system iron retention phenotype. The outward-open conformation of ferroportin was also predicted, and showed that significant conformational changes must occur in the inward- to outward-open transition of ferroportin. In particular, putative iron ligands move several ångströms away from each other, leading to the logical conclusion that the iron binding site is not occupied by the metal in the outward-open conformation of ferroportin.

• Authors: Maria C Bonaccorsi di Patti, Fabio Polticelli, Giovanna Cece, Antimo Cutone, Franco Felici, Tiziana Persichini, Giovanni Musci
• Journal: The FEBS journal (FEBS J) Vol. 281 Issue 12 Pg. 2851-60 (Jun 2014) ISSN: 1742-4658 [Electronic] England
• PMID: 24767627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: © 2014 FEBS.

Chemical References

• Cation Transport Proteins
• Escherichia coli Proteins
• Ligands
• metal transporting protein 1
• Iron

Topics

• Binding Sites
• Cation Transport Proteins (chemistry, genetics, metabolism)
• Escherichia coli Proteins (chemistry)
• HEK293 Cells
• Hemochromatosis (genetics)
• Humans
• Iron (metabolism)
• Ligands
• Models, Molecular
• Mutation
• Protein Conformation