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-Structure paper
| タイトル | Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 10559, Year 2024 |
| 掲載日 | 2024年12月4日 |
著者 | Ralf Steinhilper / Linda Boß / Sven-A Freibert / Vinzent Schulz / Nils Krapoth / Susann Kaltwasser / Roland Lill / Bonnie J Murphy / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:39632806 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.03 - 2.52 Å |
| 構造データ | ![]() EMDB-19355: Structure of the FDX2-bound core ISC complex (consensus refinement) EMDB-19356, PDB-8rmc: EMDB-19357, PDB-8rmd: ![]() EMDB-19358: Structure of the core ISC complex under turnover conditions (consensus refinement) EMDB-19359, PDB-8rme: EMDB-19360, PDB-8rmf: EMDB-19361, PDB-8rmg: |
| 化合物 | ![]() ChemComp-FE2: ![]() ChemComp-FES: ![]() ChemComp-8Q1: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | TRANSFERASE / cysteine desulfurase / FeS biosynthesis / FeS biogenesis / mitochondria / Friedreich's ataxia / frataxin / ferredoxin / FDX2 / iron-sulfur cluster |
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