8QU9

Structure of the NCOA4 (Nuclear Receptor Coactivator 4)-FTH1 (H-Ferritin) complex

8QU9 の概要

• エントリーDOI: 10.2210/pdb8qu9/pdb
• EMDBエントリー: 18658
• 分子名称: Ferritin heavy chain, NCOA4 (Nuclear Receptor Coactivator 4), FE (III) ION, ... (4 entities in total)
• 機能のキーワード: ferritinophagy, iron homeostasis, ncoa4, ferritin heavy chain, metal transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22752.91

構造登録者

Hoelzgen, F.,Klukin, E.,Zalk, R.,Shahar, A.,Cohen-Schwartz, S.,Frank, G.A. (登録日: 2023-10-15, 公開日: 2024-05-15)

主引用文献

Hoelzgen, F.,Nguyen, T.T.P.,Klukin, E.,Boumaiza, M.,Srivastava, A.K.,Kim, E.Y.,Zalk, R.,Shahar, A.,Cohen-Schwartz, S.,Meyron-Holtz, E.G.,Bou-Abdallah, F.,Mancias, J.D.,Frank, G.A.
Structural basis for the intracellular regulation of ferritin degradation.
Nat Commun, 15:3802-3802, 2024

PubMed Abstract: The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy-a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4-FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators.

PubMed: 38714719
DOI: 10.1038/s41467-024-48151-1

実験手法

ELECTRON MICROSCOPY (2.88 Å)