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Yorodumi- EMDB-0560: Structure of the human frataxin-bound iron-sulfur cluster assembl... -
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-Basic information
Entry | Database: EMDB / ID: EMD-0560 | |||||||||
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Title | Structure of the human frataxin-bound iron-sulfur cluster assembly complex | |||||||||
Map data | Human frataxin-bound iron-sulfur cluster assembly complex | |||||||||
Sample |
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Function / homology | Function and homology information negative regulation of iron ion import across plasma membrane / molybdopterin cofactor metabolic process / regulation of ferrochelatase activity / Molybdenum cofactor biosynthesis / [4Fe-4S] cluster assembly / proprioception / iron incorporation into metallo-sulfur cluster / positive regulation of lyase activity / positive regulation of succinate dehydrogenase activity / L-cysteine desulfurase complex ...negative regulation of iron ion import across plasma membrane / molybdopterin cofactor metabolic process / regulation of ferrochelatase activity / Molybdenum cofactor biosynthesis / [4Fe-4S] cluster assembly / proprioception / 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 iron-sulfur cluster assembly complex / positive regulation of aconitate hydratase activity / positive regulation of mitochondrial electron transport, NADH to ubiquinone / iron chaperone activity / cysteine desulfurase / cysteine desulfurase activity / negative regulation of organ growth / iron-sulfur cluster assembly complex / Mo-molybdopterin cofactor biosynthetic process / Mitochondrial protein import / [2Fe-2S] cluster assembly / adult walking behavior / oxidative phosphorylation / response to iron ion / embryo development ending in birth or egg hatching / iron-sulfur cluster assembly / acyl carrier activity / heme biosynthetic process / muscle cell cellular homeostasis / negative regulation of multicellular organism growth / organ growth / positive regulation of catalytic activity / ferroxidase / iron-sulfur cluster binding / negative regulation of release of cytochrome c from mitochondria / ferroxidase activity / protein autoprocessing / mitochondrion organization / ferric iron binding / ferrous iron binding / 2 iron, 2 sulfur cluster binding / 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 / iron ion binding / centrosome / positive regulation of cell population proliferation / negative regulation of apoptotic process / protein homodimerization activity / mitochondrion / zinc ion binding / nucleoplasm / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Escherichia coli (E. coli) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Fox NG / Yu X / Xidong F / Alain M / Joseph N / Claire SD / Christine B / Han S / Yue WW | |||||||||
Citation | Journal: Nat Commun / Year: 2019 Title: Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism. Authors: Nicholas G Fox / Xiaodi Yu / Xidong Feng / Henry J Bailey / Alain Martelli / Joseph F Nabhan / Claire Strain-Damerell / Christine Bulawa / Wyatt W Yue / Seungil Han / Abstract: The core machinery for de novo biosynthesis of iron-sulfur clusters (ISC), located in the mitochondria matrix, is a five-protein complex containing the cysteine desulfurase NFS1 that is activated by ...The core machinery for de novo biosynthesis of iron-sulfur clusters (ISC), located in the mitochondria matrix, is a five-protein complex containing the cysteine desulfurase NFS1 that is activated by frataxin (FXN), scaffold protein ISCU, accessory protein ISD11, and acyl-carrier protein ACP. Deficiency in FXN leads to the loss-of-function neurodegenerative disorder Friedreich's ataxia (FRDA). Here the 3.2 Å resolution cryo-electron microscopy structure of the FXN-bound active human complex, containing two copies of the NFS1-ISD11-ACP-ISCU-FXN hetero-pentamer, delineates the interactions of FXN with other component proteins of the complex. FXN binds at the interface of two NFS1 and one ISCU subunits, modifying the local environment of a bound zinc ion that would otherwise inhibit NFS1 activity in complexes without FXN. Our structure reveals how FXN facilitates ISC production through stabilizing key loop conformations of NFS1 and ISCU at the protein-protein interfaces, and suggests how FRDA clinical mutations affect complex formation and FXN activation. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0560.map.gz | 28.5 MB | EMDB map data format | |
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Header (meta data) | emd-0560-v30.xml emd-0560.xml | 21.6 KB 21.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0560_fsc.xml | 7.2 KB | Display | FSC data file |
Images | emd_0560.png | 38.4 KB | ||
Masks | emd_0560_msk_1.map | 30.5 MB | Mask map | |
Others | emd_0560_half_map_1.map.gz emd_0560_half_map_2.map.gz | 22.4 MB 22.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0560 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0560 | HTTPS FTP |
-Related structure data
Related structure data | 6nzuMC 0561C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0560.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Human frataxin-bound iron-sulfur cluster assembly complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.086 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_0560_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Human frataxin-bound iron-sulfur cluster assembly complex, half map 1
File | emd_0560_half_map_1.map | ||||||||||||
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Annotation | Human frataxin-bound iron-sulfur cluster assembly complex, half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Human frataxin-bound iron-sulfur cluster assembly complex, half map 2
File | emd_0560_half_map_2.map | ||||||||||||
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Annotation | Human frataxin-bound iron-sulfur cluster assembly complex, half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : The human frataxin-bound iron-sulfur cluster assembly complex
Entire | Name: The human frataxin-bound iron-sulfur cluster assembly complex |
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Components |
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-Supramolecule #1: The human frataxin-bound iron-sulfur cluster assembly complex
Supramolecule | Name: The human frataxin-bound iron-sulfur cluster assembly complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Molecular weight | Experimental: 186 KDa |
-Macromolecule #1: Cysteine desulfurase, mitochondrial
Macromolecule | Name: Cysteine desulfurase, mitochondrial / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: cysteine desulfurase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 44.850371 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: MLRPLYMDVQ ATTPLDPRVL DAMLPYLINY YGNPHSRTHA YGWESEAAME RARQQVASLI GADPREIIFT SGATESNNIA IKGVARFYR SRKKHLITTQ TEHKCVLDSC RSLEAEGFQV TYLPVQKSGI IDLKELEAAI QPDTSLVSVM TVNNEIGVKQ P IAEIGRIC ...String: MLRPLYMDVQ ATTPLDPRVL DAMLPYLINY YGNPHSRTHA YGWESEAAME RARQQVASLI GADPREIIFT SGATESNNIA IKGVARFYR SRKKHLITTQ TEHKCVLDSC RSLEAEGFQV TYLPVQKSGI IDLKELEAAI QPDTSLVSVM TVNNEIGVKQ P IAEIGRIC SSRKVYFHTD AAQAVGKIPL DVNDMKIDLM SISGHKIYGP KGVGAIYIRR RPRVRVEALQ SGGGQERGMR SG TVPTPLV VGLGAACEVA QQEMEYDHKR ISKLSERLIQ NIMKSLPDVV MNGDPKHHYP GCINLSFAYV EGESLLMALK DVA LSSGSA CTSASLEPSY VLRAIGTDED LAHSSIRFGI GRFTTEEEVD YTVEKCIQHV KRLREMSPLW EMVQDGIDLK SIKW TQH |
-Macromolecule #2: LYR motif-containing protein 4
Macromolecule | Name: LYR motif-containing protein 4 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 10.850562 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: SMAASSRAQV LALYRAMLRE SKRFSAYNYR TYAVRRIRDA FRENKNVKDP VEIQTLVNKA KRDLGVIRRQ VHIGQLYSTD KLIIENRDM PRT |
-Macromolecule #3: Acyl carrier protein
Macromolecule | Name: Acyl carrier protein / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Escherichia coli (E. coli) |
Molecular weight | Theoretical: 8.251055 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: MSTIEERVKK IIGEQLGVKQ EEVTNNASFV EDLGADSLDT VELVMALEEE FDTEIPDEEA EKITTVQAAI DYIN |
-Macromolecule #4: Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
Macromolecule | Name: Iron-sulfur cluster assembly enzyme ISCU, mitochondrial type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.41258 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: MYHKKVVDHY ENPRNVGSLD KTSKNVGTGL VGAPACGDVM KLQIQVDEKG KIVDARFKTF GCGSAIASSS LATEWVKGKT VEEALTIKN TDIAKELCLP PVKLHCSMLA EDAIKAALAD YKLKQ |
-Macromolecule #5: Frataxin, mitochondrial
Macromolecule | Name: Frataxin, mitochondrial / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO / EC number: ferroxidase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 14.501001 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: SMSGTLGHPG SLDETTYERL AEETLDSLAE FFEDLADKPY TFEDYDVSFG SGVLTVKLGG DLGTYVINKQ TPNKQIWLSS PSSGPKRYD WTGKNWVYSH DGVSLHELLA AELTKALKTK LDLSSLAYSG KDA |
-Macromolecule #6: PYRIDOXAL-5'-PHOSPHATE
Macromolecule | Name: PYRIDOXAL-5'-PHOSPHATE / type: ligand / ID: 6 / Number of copies: 2 / Formula: PLP |
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Molecular weight | Theoretical: 247.142 Da |
Chemical component information | ChemComp-PLP: |
-Macromolecule #7: S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-b...
Macromolecule | Name: S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate type: ligand / ID: 7 / Number of copies: 2 / Formula: 8Q1 |
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Molecular weight | Theoretical: 540.651 Da |
Chemical component information | ChemComp-8Q1: |
-Macromolecule #8: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 8 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 42.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |