Ferroportin, a membrane protein belonging to the major facilitator superfamily of transporters, is the only vertebrate iron exporter known so far. Several ferroportin mutations lead to the so-called ferroportin disease or type 4 hemochromatosis, characterized by two distinct iron accumulation phenotypes depending on whether the mutation affects the activity of the protein or its degradation pathway. Through extensive molecular modeling analyses using the structure of all known major facilitator superfamily members as templates, multiple structural models of ferroportin in the three mechanistically relevant conformations (inward open, occluded, and outward open) have been obtained. The best models, selected on the ground of experimental data available on wild-type and mutant ferroportion, provide for the first time a prediction at the atomic level of the dynamics of the transporter. Based on these results, a possible mechanism for iron export is proposed.
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1515/bams-2015-0034|
|Codice identificativo ISI:||WOS:000453250400001|
|Codice identificativo Scopus:||2-s2.0-84999274209|
|Titolo:||The human iron exporter ferroportin. Insight into the transport mechanism by molecular modeling|
|Appare nelle tipologie:||1.1 Articolo in rivista|