8qu9: Difference between revisions
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==Structure of the NCOA4 (Nuclear Receptor Coactivator 4)-FTH1 (H-Ferritin) complex== | |||
<StructureSection load='8qu9' size='340' side='right'caption='[[8qu9]], [[Resolution|resolution]] 2.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8qu9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QU9 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.88Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8qu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qu9 OCA], [https://pdbe.org/8qu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qu9 RCSB], [https://www.ebi.ac.uk/pdbsum/8qu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qu9 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Structural basis for the intracellular regulation of ferritin degradation.,Hoelzgen F, Nguyen TTP, Klukin E, Boumaiza M, Srivastava AK, Kim EY, Zalk R, Shahar A, Cohen-Schwartz S, Meyron-Holtz EG, Bou-Abdallah F, Mancias JD, Frank GA Nat Commun. 2024 May 7;15(1):3802. doi: 10.1038/s41467-024-48151-1. PMID:38714719<ref>PMID:38714719</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8qu9" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Cohen-Schwartz S]] | |||
[[Category: Frank GA]] | |||
[[Category: Hoelzgen F]] | |||
[[Category: Klukin E]] | |||
[[Category: Shahar A]] | |||
[[Category: Zalk R]] | |||
