8RME
Structure of the core ISC complex under turnover conditions (frataxin-bound)
Summary for 8RME
| Entry DOI | 10.2210/pdb8rme/pdb |
| Related | 8RMF 8RMG |
| EMDB information | 19359 |
| Descriptor | Isoform Mitochondrial of Cysteine desulfurase, LYR motif-containing protein 4, Isoform 1 of Iron-sulfur cluster assembly enzyme ISCU, ... (8 entities in total) |
| Functional Keywords | cysteine desulfurase, fes biosynthesis, fes biogenesis, mitochondria, friedreich's ataxia, frataxin, ferredoxin, fdx2, iron-sulfur cluster, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 9 |
| Total formula weight | 181743.01 |
| Authors | |
| Primary citation | Steinhilper, R.,Boss, L.,Freibert, S.A.,Schulz, V.,Krapoth, N.,Kaltwasser, S.,Lill, R.,Murphy, B.J. Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex. Nat Commun, 15:10559-10559, 2024 Cited by PubMed Abstract: Iron-sulfur (FeS) protein biogenesis in eukaryotes begins with the de novo assembly of [2Fe-2S] clusters by the mitochondrial core iron-sulfur cluster assembly (ISC) complex. This complex comprises the scaffold protein ISCU2, the cysteine desulfurase subcomplex NFS1-ISD11-ACP1, the allosteric activator frataxin (FXN) and the electron donor ferredoxin-2 (FDX2). The structural interaction of FDX2 with the complex remains unclear. Here, we present cryo-EM structures of the human FDX2-bound core ISC complex showing that FDX2 and FXN compete for overlapping binding sites. FDX2 binds in either a 'distal' conformation, where its helix F interacts electrostatically with an arginine patch of NFS1, or a 'proximal' conformation, where this interaction tightens and the FDX2-specific C terminus binds to NFS1, facilitating the movement of the [2Fe-2S] cluster of FDX2 closer to the ISCU2 FeS cluster assembly site for rapid electron transfer. Structure-based mutational studies verify the contact areas of FDX2 within the core ISC complex. PubMed: 39632806DOI: 10.1038/s41467-024-54585-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.49 Å) |
Structure validation
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