6WIK

Cryo-EM structure of SLC40/ferroportin with Fab in the presence of hepcidin

Summary for 6WIK

• Entry DOI: 10.2210/pdb6wik/pdb
• Related: 6VYH
• EMDB information: 21460 21684
• Descriptor: 11F9 Fab light-chain, 11F9 Fab heavy-chain, Solute carrier family 40 protein (3 entities in total)
• Functional Keywords: slc40, fpn, ferroportin, iron transporter, hepcidin, membrane protein
• Biological source: Carlito syrichta (Philippine tarsier); More
• Total number of polymer chains: 3
• Total formula weight: 113013.93

Authors

Shen, J.,Ren, Z.,Pan, Y.,Gao, S.,Yan, N.,Zhou, M. (deposition date: 2020-04-10, release date: 2020-11-11, Last modification date: 2025-05-14)

Primary citation

Pan, Y.,Ren, Z.,Gao, S.,Shen, J.,Wang, L.,Xu, Z.,Yu, Y.,Bachina, P.,Zhang, H.,Fan, X.,Laganowsky, A.,Yan, N.,Zhou, M.
Structural basis of ion transport and inhibition in ferroportin.
Nat Commun, 11:5686-5686, 2020

PubMed Abstract: Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron deficiency anemia. Here we present the structures of the ferroportin from the primate Philippine tarsier (TsFpn) in the presence and absence of hepcidin solved by cryo-electron microscopy. TsFpn is composed of two domains resembling a clamshell and the structure defines two metal ion binding sites, one in each domain. Both structures are in an outward-facing conformation, and hepcidin binds between the two domains and reaches one of the ion binding sites. Functional studies show that TsFpn is an electroneutral H/Fe antiporter so that transport of each Fe is coupled to transport of two H in the opposite direction. Perturbing either of the ion binding sites compromises the coupled transport of H and Fe. These results establish the structural basis of metal ion binding, transport and inhibition in ferroportin and provide a blueprint for targeting ferroportin in pharmacological intervention of ferroportin diseases.

PubMed: 33173040
DOI: 10.1038/s41467-020-19458-6

Experimental method

ELECTRON MICROSCOPY (3.4 Å)