8DL7

Cryo-EM structure of human ferroportin/slc40 bound to minihepcidin PR73 in nanodisc

8DL7 の概要

• エントリーDOI: 10.2210/pdb8dl7/pdb
• EMDBエントリー: 27498
• 関連するBIRD辞書のPRD_ID: PRD_002510
• 分子名称: Solute carrier family 40 member 1, 11F9 light-chain, 11F9 heavy-chain, ... (6 entities in total)
• 機能のキーワード: slc40, fpn, ferroportin, iron, transporter, hepcidin, minihepcidin, pr73, human, nanodisc, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 115951.90

構造登録者

Shen, J.,Wilbon, A.S.,Pan, Y.,Zhou, M. (登録日: 2022-07-07, 公開日: 2022-12-07, 最終更新日: 2025-05-21)

主引用文献

Wilbon, A.S.,Shen, J.,Ruchala, P.,Zhou, M.,Pan, Y.
Structural basis of ferroportin inhibition by minihepcidin PR73.
Plos Biol., 21:e3001936-e3001936, 2023

PubMed Abstract: Ferroportin (Fpn) is the only known iron exporter in humans and is essential for maintaining iron homeostasis. Fpn activity is suppressed by hepcidin, an endogenous peptide hormone, which inhibits iron export and promotes endocytosis of Fpn. Hepcidin deficiency leads to hemochromatosis and iron-loading anemia. Previous studies have shown that small peptides that mimic the first few residues of hepcidin, i.e., minihepcidins, are more potent than hepcidin. However, the mechanism of enhanced inhibition by minihepcidins remains unclear. Here, we report the structure of human ferroportin in complex with a minihepcidin, PR73 that mimics the first 9 residues of hepcidin, at 2.7 Å overall resolution. The structure reveals novel interactions that were not present between Fpn and hepcidin. We validate PR73-Fpn interactions through binding and transport assays. These results provide insights into how minihepcidins increase inhibition potency and will guide future development of Fpn inhibitors.

PubMed: 36649314
DOI: 10.1371/journal.pbio.3001936

実験手法

ELECTRON MICROSCOPY (2.7 Å)