Structure and mechanism of a primate ferroportin

Abstract

4Ferroportin is the only cellular iron exporter in human and essential for iron homoeostasis.

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

“…These remain to be investigated experimentally, but of note, Rishi and colleagues recently reported on the intracellular localization of ferroportin dimers, and concluded that both the carboxy-and amino-termini of the protein are intracellular [109]. As cited earlier, the details of hepcidin's own interaction sites with ferroportin remain the subject of different structural determination projects [12,18,108]. Relatedly, and of interest, Neves and colleagues, using experiments on iron overload in European bass (Dicentrarchus labrax), have discussed the functional partnership between hepcidin and ferroportin from an evolutionary perspective and suggested that this may "open new possibilities for the pharmaceutical use of selected fish […] hepcidins during infections, with no impact on iron homeostasis" [90,91].…”

“…Finally, hepcidin binds to and mediates the degradation of ferroportin (encoded by the SLC40A1 / FPN1 gene), the only known cellular iron exporter. The structural details of this interaction are being mapped and studied in ever more detail [18,88,108].…”

“…Li points out that "the primordial form of coronavirus spikes might contain S2 only" [75], and the cytoplasmic motif features highlighted in the current report do not appear to be present in other class I viral membrane fusion proteins (which include the influenza virus hemagglutinin [20,66]), although we have not performed an exhaustive search. However, a number of questions might then arise under this scenario, such as the difference between the primary localizations of hepcidin (considering its putative interaction with extracellular and transmembrane regions of ferroportin [12,18,108]) versus the CT domain of the spike protein. Alternatively, it might be argued that perhaps a case of convergent sequence evolution is at play.…”