8QU9
Structure of the NCOA4 (Nuclear Receptor Coactivator 4)-FTH1 (H-Ferritin) complex
Summary for 8QU9
| Entry DOI | 10.2210/pdb8qu9/pdb |
| EMDB information | 18658 |
| Descriptor | Ferritin heavy chain, NCOA4 (Nuclear Receptor Coactivator 4), FE (III) ION, ... (4 entities in total) |
| Functional Keywords | ferritinophagy, iron homeostasis, ncoa4, ferritin heavy chain, metal transport |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 22752.91 |
| Authors | Hoelzgen, F.,Klukin, E.,Zalk, R.,Shahar, A.,Cohen-Schwartz, S.,Frank, G.A. (deposition date: 2023-10-15, release date: 2024-05-15) |
| Primary citation | 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 Cited by 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: 38714719DOI: 10.1038/s41467-024-48151-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.88 Å) |
Structure validation
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