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Yorodumi- PDB-6nzu: Structure of the human frataxin-bound iron-sulfur cluster assembl... -
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-Basic information
Entry | Database: PDB / ID: 6nzu | ||||||
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Title | Structure of the human frataxin-bound iron-sulfur cluster assembly complex | ||||||
Components |
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Keywords | TRANSFERASE / OXIDOREDUCTASE / human frataxin-bound iron-sulfur cluster assembly complex | ||||||
Function / homology | Function and homology information Maturation of TCA enzymes and regulation of TCA cycle / 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 ...Maturation of TCA enzymes and regulation of TCA cycle / 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 / 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 / iron-sulfur cluster assembly / heme biosynthetic process / negative regulation of multicellular organism growth / organ growth / muscle cell cellular homeostasis / positive regulation of catalytic activity / ferroxidase / iron-sulfur cluster binding / negative regulation of release of cytochrome c from mitochondria / protein autoprocessing / ferroxidase activity / acyl carrier activity / 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 / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Fox, N.G. / Yu, X. / Xidong, F. / Alain, M. / Joseph, N. / Claire, S.D. / Christine, B. / Han, S. / Yue, W.W. | ||||||
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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6nzu.cif.gz | 359.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nzu.ent.gz | 293.8 KB | Display | PDB format |
PDBx/mmJSON format | 6nzu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nzu_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6nzu_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6nzu_validation.xml.gz | 51.2 KB | Display | |
Data in CIF | 6nzu_validation.cif.gz | 79.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nz/6nzu ftp://data.pdbj.org/pub/pdb/validation_reports/nz/6nzu | HTTPS FTP |
-Related structure data
Related structure data | 0560MC 0561C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 5 types, 10 molecules AEBFCGDHIJ
#1: Protein | Mass: 44850.371 Da / Num. of mol.: 2 / Fragment: UNP residues 56-457 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NFS1, NIFS, HUSSY-08 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: Q9Y697, cysteine desulfurase #2: Protein | Mass: 10850.562 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LYRM4, C6orf149, ISD11, CGI-203 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: Q9HD34 #3: Protein | Mass: 8251.055 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli (E. coli) / Gene: acpP, DQL48_09575, EOL36_14065 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: A0A437HBF4 #4: Protein | Mass: 13412.580 Da / Num. of mol.: 2 / Fragment: UNP residues 35-157 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ISCU, NIFUN Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: Q9H1K1 #5: Protein | Mass: 14501.001 Da / Num. of mol.: 2 / Fragment: UNP residues 81-210 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FXN, FRDA, X25 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: Q16595, ferroxidase |
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-Non-polymers , 3 types, 6 molecules
#6: Chemical | #7: Chemical | #8: Chemical | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: The human frataxin-bound iron-sulfur cluster assembly complex Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Molecular weight | Value: 0.186 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 42 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 267153 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building |
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