[English] 日本語
Yorodumi
- EMDB-0560: Structure of the human frataxin-bound iron-sulfur cluster assembl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-0560
TitleStructure of the human frataxin-bound iron-sulfur cluster assembly complex
Map data
SampleThe human frataxin-bound iron-sulfur cluster assembly complex
  • Cysteine desulfurase, mitochondrial
  • LYR motif-containing protein 4
  • Acyl carrier protein
  • Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
  • Frataxin, mitochondrial
  • (ligand) x 3
Function / homology
Function and homology information


Molybdenum cofactor biosynthesis / Mitochondrial iron-sulfur cluster biogenesis / Mitochondrial protein import / negative regulation of iron ion import across plasma membrane / L-cysteine desulfurase complex / regulation of ferrochelatase activity / positive regulation of succinate dehydrogenase activity / positive regulation of lyase activity / positive regulation of aconitate hydratase activity / proprioception ...Molybdenum cofactor biosynthesis / Mitochondrial iron-sulfur cluster biogenesis / Mitochondrial protein import / negative regulation of iron ion import across plasma membrane / L-cysteine desulfurase complex / regulation of ferrochelatase activity / positive regulation of succinate dehydrogenase activity / positive regulation of lyase activity / positive regulation of aconitate hydratase activity / proprioception / small molecule metabolic process / iron incorporation into metallo-sulfur cluster / [2Fe-2S] cluster assembly / sulfur amino acid metabolic process / cysteine desulfurase / positive regulation of mitochondrial electron transport, NADH to ubiquinone / cysteine desulfurase activity / molybdopterin cofactor biosynthetic process / iron chaperone activity / acyl carrier activity / negative regulation of organ growth / negative regulation of multicellular organism growth / oxidative phosphorylation / adult walking behavior / Mo-molybdopterin cofactor biosynthetic process / iron-sulfur cluster assembly / embryo development ending in birth or egg hatching / heme biosynthetic process / iron-sulfur cluster binding / response to iron ion / ferroxidase / protein autoprocessing / molecular adaptor activity / negative regulation of release of cytochrome c from mitochondria / ferroxidase activity / positive regulation of catalytic activity / aerobic respiration / ion transport / ferric iron binding / mitochondrion organization / ferrous iron binding / 2 iron, 2 sulfur cluster binding / cellular iron ion homeostasis / cellular response to hydrogen peroxide / 4 iron, 4 sulfur cluster binding / protein-containing complex assembly / pyridoxal phosphate binding / nuclear body / positive regulation of cell growth / mitochondrial matrix / iron ion binding / positive regulation of cell population proliferation / negative regulation of apoptotic process / mitochondrion / protein homodimerization activity / nucleoplasm / metal ion binding / nucleus / cytosol / cytoplasm
Pyridoxal phosphate-dependent transferase / Phosphopantetheine attachment site / Frataxin/CyaY superfamily / Frataxin conserved site / Aminotransferase class-V, pyridoxal-phosphate binding site / ACP-like superfamily / Aminotransferase class-V / Frataxin / Cysteine desulfurase / Phosphopantetheine attachment site ...Pyridoxal phosphate-dependent transferase / Phosphopantetheine attachment site / Frataxin/CyaY superfamily / Frataxin conserved site / Aminotransferase class-V, pyridoxal-phosphate binding site / ACP-like superfamily / Aminotransferase class-V / Frataxin / Cysteine desulfurase / Phosphopantetheine attachment site / Frataxin-like domain / NifU-like N terminal domain / Complex 1 protein (LYR family) / NIF system FeS cluster assembly, NifU, N-terminal / Frataxin/CyaY / Acyl carrier protein (ACP) / Aminotransferase class V domain / Phosphopantetheine attachment site. / Aminotransferases class-V pyridoxal-phosphate attachment site. / Pyridoxal phosphate-dependent transferase domain 1 / Pyridoxal phosphate-dependent transferase, major domain / Frataxin family profile. / Carrier protein (CP) domain profile. / Complex 1 LYR protein / Frataxin family signature. / Phosphopantetheine binding ACP domain / Cysteine desulfurase IscS / ISC system FeS cluster assembly, IscU scaffold
Acyl carrier protein / Frataxin, mitochondrial / Iron-sulfur cluster assembly enzyme ISCU, mitochondrial / LYR motif-containing protein 4 / Cysteine desulfurase, mitochondrial
Biological speciesHomo sapiens (human) / Escherichia coli (E. coli)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsFox NG / Yu X / Xidong F / Alain M / Joseph N / Claire SD / Christine B / Han S / Yue WW
CitationJournal: 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.
Validation ReportPDB-ID: 6nzu

SummaryFull reportAbout validation report
History
DepositionFeb 14, 2019-
Header (metadata) releaseMar 13, 2019-
Map releaseMay 22, 2019-
UpdateJul 10, 2019-
Current statusJul 10, 2019Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0425
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.0425
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: : PDB-6nzu
  • Surface level: 0.0425
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_0560.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.09 Å/pix.
x 200 pix.
= 217.2 Å
1.09 Å/pix.
x 200 pix.
= 217.2 Å
1.09 Å/pix.
x 200 pix.
= 217.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.086 Å
Density
Contour LevelBy AUTHOR: 0.0425 / Movie #1: 0.0425
Minimum - Maximum-0.20349748 - 0.33728746
Average (Standard dev.)-0.00007063915 (±0.011196485)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 217.2 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0861.0861.086
M x/y/z200200200
origin x/y/z0.0000.0000.000
length x/y/z217.200217.200217.200
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS200200200
D min/max/mean-0.2030.337-0.000

-
Supplemental data

-
Segmentation: #1

Fileemd_0560_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

-
Sample components

+
Entire The human frataxin-bound iron-sulfur cluster assembly complex

EntireName: The human frataxin-bound iron-sulfur cluster assembly complex
Number of components: 9

+
Component #1: protein, The human frataxin-bound iron-sulfur cluster assembly complex

ProteinName: The human frataxin-bound iron-sulfur cluster assembly complex
Recombinant expression: No
MassExperimental: 186 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)

+
Component #2: protein, Cysteine desulfurase, mitochondrial

ProteinName: Cysteine desulfurase, mitochondrial / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 44.850371 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)

+
Component #3: protein, LYR motif-containing protein 4

ProteinName: LYR motif-containing protein 4 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 10.850562 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)

+
Component #4: protein, Acyl carrier protein

ProteinName: Acyl carrier protein / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 8.251055 kDa
SourceSpecies: Escherichia coli (E. coli)
Source (engineered)Expression System: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)

+
Component #5: protein, Iron-sulfur cluster assembly enzyme ISCU, mitochondrial

ProteinName: Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 13.41258 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)

+
Component #6: protein, Frataxin, mitochondrial

ProteinName: Frataxin, mitochondrial / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 14.501001 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)

+
Component #7: ligand, PYRIDOXAL-5'-PHOSPHATE

LigandName: PYRIDOXAL-5'-PHOSPHATEPyridoxal phosphate / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 0.247142 kDa

+
Component #8: ligand, S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)but...

LigandName: S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate
Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 0.540651 kDa

+
Component #9: ligand, ZINC ION

LigandName: ZINC ION / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 6.540905 MDa

-
Experimental details

-
Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionpH: 7.5
Support filmunspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 42 e/Å2 / Illumination mode: FLOOD BEAM
LensImaging mode: BRIGHT FIELD
Specimen HolderModel: OTHER
CameraDetector: GATAN K2 SUMMIT (4k x 4k)

-
Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: C2 (2 fold cyclic) / Number of projections: 267153
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF
FSC plot (resolution estimation)

-
Atomic model buiding

Modeling #1Software: Coot / Refinement protocol: rigid body / Refinement space: REAL
Input PDB model: 5KZ5, 5WKP, 5WKP, 5WKP, 5WKP
Chain ID: A, A, B, C, D
Output model

+
About Yorodumi

-
News

-
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force. (see PDBe EMDB page)
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.: Q: What is "EMD"? / ID/Accession-code notation in Yorodumi/EM Navigator

External links: EMDB at PDBe / Contact to PDBj

-
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.

External links: wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

Read more

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.

Related info.: EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more