{"doi":"10.1101/2020.03.04.975748","title":"Structure and mechanism of a primate ferroportin","abstract":"Abstract Ferroportin is the only cellular iron exporter in human and essential for iron homoeostasis. Mutations in ferroportin are associated with hemochromatosis or ferroportin diseases characterized by a paradoxical combination of anemia and abnormal accumulation of iron in cells. Ferroportin is also the target of hepcidin, which is a hormone that downregulates ferroportin activity. However, due to a lack of three-dimensional structures, the mechanism of iron transport by ferroportin and its regulation by hepcidin remains unclear. Here we present the structure of a ferroportin from the primate Philippine tarsier (TsFpn) at 3.0 Å resolution determined by cryo-electron microscopy. TsFpn has a structural fold common to major facilitator superfamily of transporters and the current structure is in an outward-open conformation. The structure identifies two potential ion binding sites with each site coordinated by two residues. Functional studies demonstrate that TsFpn is a H + /Fe 2+ antiporter and that transport of one Fe 2+ is coupled to the transport of two H + in the opposite direction such that the transport cycle is electroneutral. Further studies show that the two ion binding sites affect transport of H + and Fe 2+ differently. The structure also provides mechanistic interpretation for mutations that cause ferroportin diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126338,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":296080,"name":"Shuai Gao","orcid":"0000-0002-8734-2489","position":1,"is_corresponding":false},{"id":297716,"name":"Jiemin Shen","orcid":"0000-0002-3977-0681","position":2,"is_corresponding":false},{"id":297717,"name":"Lie Wang","orcid":"0000-0002-9406-5168","position":3,"is_corresponding":false},{"id":299992,"name":"Zhichun Xu","orcid":null,"position":4,"is_corresponding":false},{"id":297718,"name":"Ye Yu","orcid":"0000-0002-4054-8543","position":5,"is_corresponding":false},{"id":297719,"name":"Preetham Bachina","orcid":"0000-0001-9833-4487","position":6,"is_corresponding":false},{"id":299993,"name":"Hanzhi Zhang","orcid":null,"position":7,"is_corresponding":false},{"id":297720,"name":"Arthur Laganowsky","orcid":"0000-0001-5012-5547","position":8,"is_corresponding":false},{"id":256562,"name":"Nieng Yan","orcid":"0000-0003-4829-7416","position":9,"is_corresponding":false},{"id":297721,"name":"Ming Zhou","orcid":"0000-0001-7198-165X","position":10,"is_corresponding":false},{"id":297715,"name":"Yaping Pan","orcid":"0000-0001-7459-4217","position":11,"is_corresponding":false},{"id":299991,"name":"Zhenning Ren","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:15:23.509897Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}