6WIK

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

6WIK の概要

• エントリーDOI: 10.2210/pdb6wik/pdb
• 関連するPDBエントリー: 6VYH
• EMDBエントリー: 21460 21684
• 分子名称: 11F9 Fab light-chain, 11F9 Fab heavy-chain, Solute carrier family 40 protein (3 entities in total)
• 機能のキーワード: slc40, fpn, ferroportin, iron transporter, hepcidin, membrane protein
• 由来する生物種: Carlito syrichta (Philippine tarsier); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 113013.93

構造登録者

Shen, J.,Ren, Z.,Pan, Y.,Gao, S.,Yan, N.,Zhou, M. (登録日: 2020-04-10, 公開日: 2020-11-11, 最終更新日: 2025-05-14)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.4 Å)