23PG

Cryo-EM structure of human ABCB7 in complex with CoPP:GSH/ADPVO4

23PG の概要

• エントリーDOI: 10.2210/pdb23pg/pdb
• 関連するPDBエントリー: 7VGF
• EMDBエントリー: 69143
• 分子名称: Iron-sulfur clusters transporter ABCB7, mitochondrial, PROTOPORPHYRIN IX CONTAINING CO, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: abcb7, heme exporter, x-linked sideroblastic anemia with ataxia, cobalt protoporphyrin ix, iron-sulfur (fe-s) cluster, glutathione, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 159971.17

構造登録者

Ju, S.,Choi, S.H.,Lee, H.Y.,Jin, M.S. (登録日: 2026-02-12, 公開日: 2026-06-03)

主引用文献

Ju, S.,Choi, S.H.,Lee, H.Y.,Jin, M.S.
Cryo-EM structures of human ABCB7 reveal the molecular basis of mitochondrial matrix heme export.
Commun Biol, 2026

PubMed Abstract: ATP-binding cassette transporter subfamily B member 7 (ABCB7) is a mitochondrial ATP-driven pump essential for cytosolic iron-sulfur (Fe-S) cluster biogenesis and cellular iron homeostasis. Mutations in ABCB7 are linked to X-linked sideroblastic anemia with ataxia (XLSA/A). Here, we demonstrate that the ATPase activity of ABCB7 is stimulated by iron and cobalt protoporphyrin IX (hemin and CoPP) in the presence of glutathione (GSH), highlighting an additional role for ABCB7 as a metalloporphyrin exporter. Using single-particle cryo-electron microscopy, we determine the structures of human ABCB7 in multiple functional states at resolutions of up to 2.3 Å. Our structures reveal a putative substrate-binding cavity that accommodates two stacked CoPP molecules conjugated by two GSH cysteine thiols. The conserved residue F426 controls substrate entrapment and release as a molecular gate. We further show that at high substrate concentrations excess CoPP easily partitions into the lipid bilayer, where the hydrophobic environment stabilizes the porphyrin macrocycle and limits the aggregation or redox reactivity that is prone to occur with free porphyrins in aqueous solution. Finally, our structure analyses rationalize the pathogenic effect of the E433K mutation associated with XLSA/A disease.

PubMed: 42103889
DOI: 10.1038/s42003-026-10223-x

実験手法

ELECTRON MICROSCOPY (2.87 Å)