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基本情報
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タイトル | Structure of the human mitochondrial iron-sulfur cluster biosynthesis complex during persulfide transfer (persulfide on NFS1 and ISCU2) | |||||||||
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![]() | cysteine desulfurase / FeS biosynthesis / FeS biogenesis / mitochondria / Friedreich's ataxia / persulfide / frataxin / TRANSFERASE | |||||||||
機能・相同性 | ![]() regulation of ferrochelatase activity / negative regulation of iron ion import across plasma membrane / molybdopterin cofactor metabolic process / Molybdenum cofactor biosynthesis / proprioception / [4Fe-4S] cluster assembly / iron incorporation into metallo-sulfur cluster / positive regulation of lyase activity / positive regulation of succinate dehydrogenase activity / L-cysteine desulfurase complex ...regulation of ferrochelatase activity / negative regulation of iron ion import across plasma membrane / molybdopterin cofactor metabolic process / Molybdenum cofactor biosynthesis / proprioception / [4Fe-4S] cluster assembly / iron incorporation into metallo-sulfur cluster / positive regulation of lyase activity / positive regulation of succinate dehydrogenase activity / L-cysteine desulfurase complex / Mitochondrial iron-sulfur cluster biogenesis / mitochondrial [2Fe-2S] assembly complex / positive regulation of aconitate hydratase activity / Maturation of TCA enzymes and regulation of TCA cycle / positive regulation of mitochondrial electron transport, NADH to ubiquinone / iron chaperone activity / cysteine desulfurase / cysteine desulfurase activity / negative regulation of organ growth / Mo-molybdopterin cofactor biosynthetic process / iron-sulfur cluster assembly complex / Mitochondrial protein import / [2Fe-2S] cluster assembly / oxidative phosphorylation / adult walking behavior / response to iron ion / embryo development ending in birth or egg hatching / lipid biosynthetic process / iron-sulfur cluster assembly / heme biosynthetic process / negative regulation of multicellular organism growth / lipid A biosynthetic process / organ growth / positive regulation of catalytic activity / muscle cell cellular homeostasis / ferroxidase / negative regulation of release of cytochrome c from mitochondria / iron-sulfur cluster binding / phosphopantetheine binding / protein autoprocessing / acyl binding / ferroxidase activity / acyl carrier activity / ferric iron binding / mitochondrion organization / ferrous iron binding / 2 iron, 2 sulfur cluster binding / fatty acid biosynthetic process / cellular response to hydrogen peroxide / pyridoxal phosphate binding / Maturation of replicase proteins / iron ion transport / positive regulation of cell growth / intracellular iron ion homeostasis / molecular adaptor activity / nuclear body / mitochondrial matrix / response to xenobiotic stimulus / iron ion binding / centrosome / lipid binding / positive regulation of cell population proliferation / negative regulation of apoptotic process / protein homodimerization activity / mitochondrion / zinc ion binding / nucleoplasm / nucleus / metal ion binding / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.58 Å | |||||||||
![]() | Steinhilper R / Murphy BJ | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2. 著者: Vinzent Schulz / Ralf Steinhilper / Jonathan Oltmanns / Sven-A Freibert / Nils Krapoth / Uwe Linne / Sonja Welsch / Maren H Hoock / Volker Schünemann / Bonnie J Murphy / Roland Lill / ![]() 要旨: Maturation of iron-sulfur proteins in eukaryotes is initiated in mitochondria by the core iron-sulfur cluster assembly (ISC) complex, consisting of the cysteine desulfurase sub-complex NFS1-ISD11- ...Maturation of iron-sulfur proteins in eukaryotes is initiated in mitochondria by the core iron-sulfur cluster assembly (ISC) complex, consisting of the cysteine desulfurase sub-complex NFS1-ISD11-ACP1, the scaffold protein ISCU2, the electron donor ferredoxin FDX2, and frataxin, a protein dysfunctional in Friedreich's ataxia. The core ISC complex synthesizes [2Fe-2S] clusters de novo from Fe and a persulfide (SSH) bound at conserved cluster assembly site residues. Here, we elucidate the poorly understood Fe-dependent mechanism of persulfide transfer from cysteine desulfurase NFS1 to ISCU2. High-resolution cryo-EM structures obtained from anaerobically prepared samples provide snapshots that both visualize different stages of persulfide transfer from Cys381 to Cys138 and clarify the molecular role of frataxin in optimally positioning assembly site residues for fast sulfur transfer. Biochemical analyses assign ISCU2 residues essential for sulfur transfer, and reveal that Cys138 rapidly receives the persulfide without a detectable intermediate. Mössbauer spectroscopy assessing the Fe coordination of various sulfur transfer intermediates shows a dynamic equilibrium between pre- and post-sulfur-transfer states shifted by frataxin. Collectively, our study defines crucial mechanistic stages of physiological [2Fe-2S] cluster assembly and clarifies frataxin's molecular role in this fundamental process. | |||||||||
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マップデータ | ![]() | 4.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.7 KB 20.7 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 7.4 KB | 表示 | ![]() |
画像 | ![]() | 74.5 KB | ||
マスクデータ | ![]() | 34.3 MB | ![]() | |
Filedesc metadata | ![]() | 7 KB | ||
その他 | ![]() ![]() | 26.4 MB 26.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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関連構造データ | ![]() 8pk9MC ![]() 8pk8C ![]() 8pkaC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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「今月の分子」の関連する項目 |
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マップ
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ボクセルのサイズ | X=Y=Z: 1.03 Å | ||||||||||||||||||||
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_17733_half_map_1.map | ||||||||||||
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_17733_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
+全体 : Iron-bound human NFS1-ISD11-ACP1-ISCU2-FXN (Fe-NIAUX) complex dur...
+超分子 #1: Iron-bound human NFS1-ISD11-ACP1-ISCU2-FXN (Fe-NIAUX) complex dur...
+分子 #1: Cysteine desulfurase
+分子 #2: LYR motif-containing protein 4
+分子 #3: Acyl carrier protein
+分子 #4: Iron-sulfur cluster assembly enzyme ISCU
+分子 #5: Frataxin mature form
+分子 #6: PYRIDOXAL-5'-PHOSPHATE
+分子 #7: S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-b...
+分子 #8: FE (II) ION
+分子 #9: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 62.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |