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- EMDB-17734: Structure of the human mitochondrial iron-sulfur cluster biosynth... -
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Open data
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Basic information
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Title | Structure of the human mitochondrial iron-sulfur cluster biosynthesis complex during persulfide transfer (without frataxin) | |||||||||
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Function / homology | ![]() negative regulation of iron ion import across plasma membrane / molybdopterin cofactor metabolic process / Molybdenum cofactor biosynthesis / [4Fe-4S] cluster assembly / iron incorporation into metallo-sulfur cluster / L-cysteine desulfurase complex / Mitochondrial iron-sulfur cluster biogenesis / mitochondrial [2Fe-2S] assembly complex / positive regulation of aconitate hydratase activity / positive regulation of mitochondrial electron transport, NADH to ubiquinone ...negative regulation of iron ion import across plasma membrane / molybdopterin cofactor metabolic process / Molybdenum cofactor biosynthesis / [4Fe-4S] cluster assembly / iron incorporation into metallo-sulfur cluster / L-cysteine desulfurase complex / Mitochondrial iron-sulfur cluster biogenesis / mitochondrial [2Fe-2S] assembly complex / positive regulation of aconitate hydratase activity / positive regulation of mitochondrial electron transport, NADH to ubiquinone / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
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![]() | Steinhilper R / Murphy BJ | |||||||||
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![]() | ![]() Title: Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2. Authors: 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 / ![]() Abstract: 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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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.9 KB 20.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.4 KB | Display | ![]() |
Images | ![]() | 66.6 KB | ||
Masks | ![]() | 34.3 MB | ![]() | |
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 26.4 MB 26.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8pkaMC ![]() 8pk8C ![]() 8pk9C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #1
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Sample components
+Entire : Iron-bound human NFS1-ISD11-ACP1-ISCU2-FXN (Fe-NIAUX) complex dur...
+Supramolecule #1: Iron-bound human NFS1-ISD11-ACP1-ISCU2-FXN (Fe-NIAUX) complex dur...
+Supramolecule #2: Cysteine desulfurase, LYR motif-containing protein 4 and Iron-sul...
+Supramolecule #3: Acyl carrier protein
+Macromolecule #1: Cysteine desulfurase
+Macromolecule #2: LYR motif-containing protein 4
+Macromolecule #3: Acyl carrier protein
+Macromolecule #4: Iron-sulfur cluster assembly enzyme ISCU
+Macromolecule #5: PYRIDOXAL-5'-PHOSPHATE
+Macromolecule #6: S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-b...
+Macromolecule #7: FE (II) ION
+Macromolecule #8: water
-Experimental details
-Structure determination
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 62.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |