8RME

Structure of the core ISC complex under turnover conditions (frataxin-bound)

8RME の概要

• エントリーDOI: 10.2210/pdb8rme/pdb
• 関連するPDBエントリー: 8RMF 8RMG
• EMDBエントリー: 19359
• 分子名称: Isoform Mitochondrial of Cysteine desulfurase, LYR motif-containing protein 4, Isoform 1 of Iron-sulfur cluster assembly enzyme ISCU, ... (8 entities in total)
• 機能のキーワード: cysteine desulfurase, fes biosynthesis, fes biogenesis, mitochondria, friedreich's ataxia, frataxin, ferredoxin, fdx2, iron-sulfur cluster, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 181743.01

構造登録者

Steinhilper, R.,Murphy, B.J. (登録日: 2024-01-05, 公開日: 2024-12-18)

主引用文献

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

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: 39632806
DOI: 10.1038/s41467-024-54585-4
主引用文献が同じPDBエントリー

実験手法

ELECTRON MICROSCOPY (2.49 Å)