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- EMDB-6776: Cryo-EM architecture of human respiratory chain megacomplex-I2III2IV2 -

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Basic information

Entry
Database: EMDB / ID: EMD-6776
TitleCryo-EM architecture of human respiratory chain megacomplex-I2III2IV2
Map data
Sample
  • Complex: Human respiratory chain megacomplex-I2III2IV2
Function / homology
Function and homology information


Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / subthalamus development / pons development / Complex III assembly ...Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / Complex III assembly / subthalamus development / pons development / Complex III assembly / Complex III assembly / pyramidal neuron development / cerebellar Purkinje cell layer development / Complex IV assembly / Complex I biogenesis / protein lipoylation / TP53 Regulates Metabolic Genes / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / Cytoprotection by HMOX1 / respiratory chain complex IV assembly / response to mercury ion / mitochondrial [2Fe-2S] assembly complex / Respiratory electron transport / protein insertion into mitochondrial inner membrane / mitochondrial respiratory chain complex III assembly / mitochondrial respirasome assembly / thalamus development / blastocyst hatching / respiratory chain complex III / respiratory chain complex IV / Mitochondrial protein import / regulation of oxidative phosphorylation / ubiquinone-6 biosynthetic process / Respiratory electron transport / cellular response to oxygen levels / : / iron-sulfur cluster assembly complex / : / : / mitochondrial large ribosomal subunit binding / response to alkaloid / gliogenesis / oxidative phosphorylation / cytochrome-c oxidase / oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor / quinol-cytochrome-c reductase / response to copper ion / neural precursor cell proliferation / cardiac muscle tissue development / ubiquinol-cytochrome-c reductase activity / response to glucagon / [2Fe-2S] cluster assembly / oxygen sensor activity / mitochondrial electron transport, cytochrome c to oxygen / cellular respiration / midbrain development / azurophil granule membrane / : / cytochrome-c oxidase activity / hypothalamus development / mitochondrial electron transport, ubiquinol to cytochrome c / ubiquinone binding / sodium ion transport / iron-sulfur cluster assembly / response to cobalamin / Mitochondrial protein degradation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase activity / mitochondrial ATP synthesis coupled electron transport / respiratory chain complex I / : / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / endopeptidase activator activity / RHOG GTPase cycle / electron transport coupled proton transport / acyl binding / response to hyperoxia / animal organ regeneration / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / cellular response to interferon-beta / ATP synthesis coupled electron transport / quinone binding / response to cadmium ion / : / enzyme regulator activity / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / response to cAMP / ionotropic glutamate receptor binding / Mitochondrial protein degradation / substantia nigra development / aerobic respiration / neurogenesis / respiratory electron transport chain / cerebellum development
Similarity search - Function
Cytochrome b-c1 complex subunit 10 / Single alpha-helix domain superfamily / Ubiquinol-cytochrome C reductase complex, 6.4kD protein / Cytochrome c oxidase, subunit 8 / Cytochrome c oxidase, subunit 8 superfamily / Cytochrome oxidase c subunit VIII / Cytochrome c oxidase subunit VIIa, metazoa / Cytochrome C oxidase, subunit VIIB / Cytochrome c oxidase subunit IV / Cytochrome C oxidase, subunit VIIB domain superfamily ...Cytochrome b-c1 complex subunit 10 / Single alpha-helix domain superfamily / Ubiquinol-cytochrome C reductase complex, 6.4kD protein / Cytochrome c oxidase, subunit 8 / Cytochrome c oxidase, subunit 8 superfamily / Cytochrome oxidase c subunit VIII / Cytochrome c oxidase subunit VIIa, metazoa / Cytochrome C oxidase, subunit VIIB / Cytochrome c oxidase subunit IV / Cytochrome C oxidase, subunit VIIB domain superfamily / Mitochondrial cytochrome c oxidase subunit VIc/VIIs / Cytochrome c oxidase, subunit VIIa superfamily / Mitochondrial cytochrome c oxidase subunit VIc/VIIs superfamily / : / Cytochrome c oxidase subunit VIc / Cytochrome C oxidase chain VIIB / Cytochrome c oxidase, subunit VIa, conserved site / Cytochrome c oxidase subunit VIa signature. / Ubiquinol-cytochrome c reductase 8kDa, N-terminal / Ubiquinol-cytochrome c reductase 8 kDa, N-terminal / Cytochrome c oxidase, subunit VIb / : / Cytochrome c oxidase, subunit VIa / Cytochrome c oxidase, subunit VIa superfamily / Cytochrome c oxidase subunit VIa / Cytochrome c oxidase, subunit VIb superfamily / Cytochrome c oxidase subunit 2, C-terminal / Cytochrome oxidase c subunit VIb / Cytochrome c oxidase subunit Vb, zinc binding region signature. / Cytochrome c oxidase subunit VIIc / Cytochrome c oxidase subunit IV family / Cytochrome c oxidase subunit VIIc superfamily / Cytochrome c oxidase subunit IV superfamily / Cytochrome c oxidase subunit VIIc / Cytochrome c oxidase subunit IV / Cytochrome c oxidase, subunit Va/VI / Cytochrome c oxidase, subunit Va/VI superfamily / Cytochrome c oxidase subunit Va / Cytochrome c oxidase subunit VII / Cytochrome c oxidase subunit VII / Cytochrome b-c1 complex, subunit 6 / Globular protein, non-globular alpha/beta subunit / Cytochrome c oxidase subunit III domain / Cytochrome c oxidase, subunit Vb / Cytochrome c oxidase, subunit Vb superfamily / Cytochrome c oxidase subunit Vb / Cytochrome c oxidase subunit Vb, zinc binding domain profile. / Cytochrome c oxidase, subunit II / Cytochrome c oxidase subunit I domain / Cytochrome C oxidase subunit II, transmembrane domain / Complex1_LYR-like / Cytochrome b-c1 complex subunit 8 / UcrQ family / Cytochrome C oxidase subunit II, transmembrane domain / Cytochrome oxidase subunit II transmembrane region profile. / Cytochrome bc1 complex subunit Rieske, transmembrane domain superfamily / Cytochrome b-c1 complex subunit 7 / Cytochrome b-c1 complex subunit 7 superfamily / Ubiquinol-cytochrome C reductase complex 14kD subunit / Cytochrome c oxidase subunit III / Cytochrome c oxidase subunit III-like / Cytochrome c oxidase, subunit III, 4-helical bundle / Cytochrome c oxidase subunit III / Heme-copper oxidase subunit III family profile. / Cytochrome c oxidase subunit III-like superfamily / Cytochrome b-c1 complex subunit 9 / Cytochrome b-c1 complex subunit 8 superfamily / Cytochrome b-c1 complex subunit 9 superfamily / Ubiquinol-cytochrome C reductase, UQCRX/QCR9 like / Cytochrome b-c1 complex subunit Rieske, transmembrane domain / Ubiquinol cytochrome reductase transmembrane region / Ubiquinol-cytochrome C reductase hinge domain / Ubiquinol-cytochrome C reductase hinge domain superfamily / Ubiquinol-cytochrome C reductase hinge protein / Cytochrome c1, transmembrane anchor, C-terminal / Cytochrome c/quinol oxidase subunit II / : / Cytochrome b / Copper centre Cu(A) / CO II and nitrous oxide reductase dinuclear copper centers signature. / Cytochrome C oxidase subunit II, transmembrane domain superfamily / : / Ubiquinol-cytochrome c reductase, iron-sulphur subunit / Cytochrome c1 / Cytochrome C1 family / : / Cytochrome b/b6, C-terminal / Cytochrome b(C-terminal)/b6/petD / Cytochrome b/b6 C-terminal region profile. / NADH:ubiquinone oxidoreductase, subunit NDUFB4 / : / Cytochrome c oxidase, subunit I, copper-binding site / Heme-copper oxidase catalytic subunit, copper B binding region signature. / NADH-ubiquinone oxidoreductase 1 subunit C1 / Cytochrome b/b6, C-terminal domain superfamily / Cytochrome b/b6/petB / NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial / Cytochrome c oxidase-like, subunit I domain / Cytochrome oxidase subunit I profile. / NADH:ubiquinone oxidoreductase, ESSS subunit
Similarity search - Domain/homology
NADH-ubiquinone oxidoreductase chain 4 / NADH-ubiquinone oxidoreductase chain 3 / NADH-ubiquinone oxidoreductase chain 1 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial / Acyl carrier protein, mitochondrial / Cytochrome b-c1 complex subunit 8 / Cytochrome b-c1 complex subunit 10 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial ...NADH-ubiquinone oxidoreductase chain 4 / NADH-ubiquinone oxidoreductase chain 3 / NADH-ubiquinone oxidoreductase chain 1 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial / Acyl carrier protein, mitochondrial / Cytochrome b-c1 complex subunit 8 / Cytochrome b-c1 complex subunit 10 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 / NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial / NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial / NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 / NADH dehydrogenase [ubiquinone] 1 subunit C2 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 / Cytochrome b / Cytochrome c oxidase subunit 1 / Cytochrome c oxidase subunit 3 / Cytochrome c oxidase subunit 4 isoform 1, mitochondrial / Cytochrome c oxidase subunit 5A, mitochondrial / Cytochrome c oxidase subunit 5B, mitochondrial / Cytochrome c oxidase subunit 6B1 / Cytochrome c oxidase subunit 7C, mitochondrial / NADH-ubiquinone oxidoreductase chain 2 / NADH-ubiquinone oxidoreductase chain 4 / NADH-ubiquinone oxidoreductase chain 5 / Cytochrome c oxidase subunit 6C / Cytochrome c oxidase subunit 7A1, mitochondrial / Cytochrome c oxidase subunit 6A2, mitochondrial / Cytochrome b-c1 complex subunit 6, mitochondrial / Cytochrome c1, heme protein, mitochondrial / Cytochrome c oxidase subunit 8B, mitochondrial / Cytochrome c oxidase subunit 7B, mitochondrial / Cytochrome b-c1 complex subunit 7 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 / NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial / Cytochrome b-c1 complex subunit 2, mitochondrial / NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial / Cytochrome b-c1 complex subunit 1, mitochondrial / Cytochrome b-c1 complex subunit Rieske, mitochondrial / NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 / NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 / Cytochrome c oxidase subunit 2 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial / NADH-ubiquinone oxidoreductase chain 2 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 / NADH-ubiquinone oxidoreductase chain 6 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 / Cytochrome b-c1 complex subunit 9 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 / NADH-ubiquinone oxidoreductase chain 4L / NADH-ubiquinone oxidoreductase chain 5
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 17.4 Å
AuthorsGu J / Wu M / Yang M
CitationJournal: Cell / Year: 2017
Title: Architecture of Human Mitochondrial Respiratory Megacomplex IIIIIV.
Authors: Runyu Guo / Shuai Zong / Meng Wu / Jinke Gu / Maojun Yang /
Abstract: The respiratory megacomplex represents the highest-order assembly of respiratory chain complexes, and it allows mitochondria to respond to energy-requiring conditions. To understand its architecture, ...The respiratory megacomplex represents the highest-order assembly of respiratory chain complexes, and it allows mitochondria to respond to energy-requiring conditions. To understand its architecture, we examined the human respiratory chain megacomplex-IIIIIV (MCIIIIIV) with 140 subunits and a subset of associated cofactors using cryo-electron microscopy. The MCIIIIIV forms a circular structure with the dimeric CIII located in the center, where it is surrounded by two copies each of CI and CIV. Two cytochrome c (Cyt.c) molecules are positioned to accept electrons on the surface of the c state CIII dimer. Analyses indicate that CII could insert into the gaps between CI and CIV to form a closed ring, which we termed the electron transport chain supercomplex. The structure not only reveals the precise assignment of individual subunits of human CI and CIII, but also enables future in-depth analysis of the electron transport chain as a whole.
History
DepositionJun 18, 2017-
Header (metadata) releaseSep 13, 2017-
Map releaseSep 13, 2017-
UpdateDec 13, 2017-
Current statusDec 13, 2017Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0056
  • Imaged by UCSF Chimera
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  • Surface view colored by height
  • Surface level: 0.0056
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-5xti
  • Surface level: 0.0056
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
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Supplemental images

Downloads & links

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Map

FileDownload / File: emd_6776.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 480 pix.
= 519.84 Å
1.08 Å/pix.
x 480 pix.
= 519.84 Å
1.08 Å/pix.
x 480 pix.
= 519.84 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.083 Å
Density
Contour LevelBy AUTHOR: 0.0056 / Movie #1: 0.0056
Minimum - Maximum-0.029248776 - 0.054389697
Average (Standard dev.)0.00030900445 (±0.005835759)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 519.83997 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0831.0831.083
M x/y/z480480480
origin x/y/z0.0000.0000.000
length x/y/z519.840519.840519.840
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS480480480
D min/max/mean-0.0290.0540.000

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Supplemental data

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Sample components

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Entire : Human respiratory chain megacomplex-I2III2IV2

EntireName: Human respiratory chain megacomplex-I2III2IV2
Components
  • Complex: Human respiratory chain megacomplex-I2III2IV2

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Supramolecule #1: Human respiratory chain megacomplex-I2III2IV2

SupramoleculeName: Human respiratory chain megacomplex-I2III2IV2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#70
Source (natural)Organism: Homo sapiens (human)
Molecular weightExperimental: 2.9 MDa

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 1.25 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: CTFFIND (ver. 3.0)
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 17.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 1.4) / Number images used: 8600
Initial angle assignmentType: RANDOM ASSIGNMENT / Software - Name: RELION (ver. 1.4)
Final angle assignmentType: RANDOM ASSIGNMENT / Software - Name: RELION (ver. 1.4)

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