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Yorodumi- PDB-8q0j: Inward-facing, slack proteoliposome complex I at 3.8 A. Initially... -
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-Basic information
Entry | Database: PDB / ID: 8q0j | |||||||||
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Title | Inward-facing, slack proteoliposome complex I at 3.8 A. Initially purified in DDM. | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Complex I / Oxidoreductase / Proteoliposomes / Membrane-bound / metabolism | |||||||||
Function / homology | Function and homology information Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / ubiquinone-6 biosynthetic process / Respiratory electron transport / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / [2Fe-2S] cluster assembly ...Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / ubiquinone-6 biosynthetic process / Respiratory electron transport / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / [2Fe-2S] cluster assembly / oxygen sensor activity / cellular respiration / Neutrophil degranulation / ubiquinone binding / Mitochondrial protein degradation / NADH:ubiquinone reductase (H+-translocating) / apoptotic mitochondrial changes / NADH dehydrogenase activity / mitochondrial ATP synthesis coupled electron transport / respiratory chain complex I / : / mitochondrial respiratory chain complex I assembly / mitochondrial electron transport, NADH to ubiquinone / electron transport coupled proton transport / acyl binding / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / ATP synthesis coupled electron transport / quinone binding / ATP metabolic process / response to cAMP / aerobic respiration / neurogenesis / respiratory electron transport chain / reactive oxygen species metabolic process / regulation of mitochondrial membrane potential / fatty acid binding / mitochondrial membrane / electron transport chain / brain development / regulation of protein phosphorylation / mitochondrial intermembrane space / fatty acid biosynthetic process / 2 iron, 2 sulfur cluster binding / positive regulation of fibroblast proliferation / NAD binding / FMN binding / 4 iron, 4 sulfur cluster binding / response to oxidative stress / mitochondrial inner membrane / oxidoreductase activity / mitochondrial matrix / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / protein-containing complex binding / apoptotic process / mitochondrion / nucleoplasm / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Grba, D.N. / Hirst, J. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Science / Year: 2024 Title: Molecular mechanism of the ischemia-induced regulatory switch in mammalian complex I. Authors: Daniel N Grba / John J Wright / Zhan Yin / William Fisher / Judy Hirst / Abstract: Respiratory complex I is an efficient driver for oxidative phosphorylation in mammalian mitochondria, but its uncontrolled catalysis under challenging conditions leads to oxidative stress and ...Respiratory complex I is an efficient driver for oxidative phosphorylation in mammalian mitochondria, but its uncontrolled catalysis under challenging conditions leads to oxidative stress and cellular damage. Ischemic conditions switch complex I from rapid, reversible catalysis into a dormant state that protects upon reoxygenation, but the molecular basis for the switch is unknown. We combined precise biochemical definition of complex I catalysis with high-resolution cryo-electron microscopy structures in the phospholipid bilayer of coupled vesicles to reveal the mechanism of the transition into the dormant state, modulated by membrane interactions. By implementing a versatile membrane system to unite structure and function, attributing catalytic and regulatory properties to specific structural states, we define how a conformational switch in complex I controls its physiological roles. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8q0j.cif.gz | 1.5 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8q0j.ent.gz | 1.2 MB | Display | PDB format |
PDBx/mmJSON format | 8q0j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8q0j_validation.pdf.gz | 2.7 MB | Display | wwPDB validaton report |
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Full document | 8q0j_full_validation.pdf.gz | 2.8 MB | Display | |
Data in XML | 8q0j_validation.xml.gz | 213.5 KB | Display | |
Data in CIF | 8q0j_validation.cif.gz | 315.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/q0/8q0j ftp://data.pdbj.org/pub/pdb/validation_reports/q0/8q0j | HTTPS FTP |
-Related structure data
Related structure data | 18054MC 8q0aC 8q0fC 8q0mC 8q0oC 8q0qC 8q1pC 8q1uC 8q1yC 8q25C 8q45C 8q46C 8q47C 8q48C 8q49C 8q4aC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-NADH-ubiquinone oxidoreductase chain ... , 7 types, 7 molecules AHJKLMN
#1: Protein | Mass: 13086.531 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: Q7JAS9, NADH:ubiquinone reductase (H+-translocating) |
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#8: Protein | Mass: 35716.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P03887 |
#10: Protein | Mass: 19110.488 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P03924, NADH:ubiquinone reductase (H+-translocating) |
#11: Protein | Mass: 10828.195 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P03902, NADH:ubiquinone reductase (H+-translocating) |
#12: Protein | Mass: 68355.930 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P03920, NADH:ubiquinone reductase (H+-translocating) |
#13: Protein | Mass: 52158.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P03910, NADH:ubiquinone reductase (H+-translocating) |
#14: Protein | Mass: 39302.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P03892, NADH:ubiquinone reductase (H+-translocating) |
-NADH dehydrogenase [ubiquinone] iron-sulfur protein ... , 7 types, 7 molecules BCDIQRe
#2: Protein | Mass: 23802.926 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P42026, NADH:ubiquinone reductase (H+-translocating) |
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#3: Protein | Mass: 30323.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P23709, NADH:ubiquinone reductase (H+-translocating) |
#4: Protein | Mass: 52678.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P17694, NADH:ubiquinone reductase (H+-translocating) |
#9: Protein | Mass: 23926.400 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P42028, NADH:ubiquinone reductase (H+-translocating) |
#17: Protein | Mass: 19841.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02375 |
#18: Protein | Mass: 13433.194 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P23934 |
#30: Protein | Mass: 12694.671 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02379 |
-NADH dehydrogenase [ubiquinone] flavoprotein ... , 3 types, 3 molecules EFs
#5: Protein | Mass: 27341.496 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P04394, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
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#6: Protein | Mass: 50718.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P25708, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
#44: Protein | Mass: 11874.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P25712 |
-Protein , 2 types, 3 molecules GTU
#7: Protein | Mass: 79532.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) References: UniProt: P15690, NADH:ubiquinone reductase (H+-translocating) |
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#20: Protein | Mass: 17421.340 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P52505 |
-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 12 types, 12 molecules OPSVWXYZabqr
#15: Protein | Mass: 39330.984 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P34942 |
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#16: Protein | Mass: 42913.430 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P34943 |
#19: Protein | Mass: 11097.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02370 |
#21: Protein | Mass: 13334.608 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P23935 |
#22: Protein | Mass: 15083.544 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02366 |
#23: Protein | Mass: 20124.133 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P42029 |
#24: Protein | Mass: 14772.021 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q8HXG6 |
#25: Protein | Mass: 16694.395 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q95KV7 |
#26: Protein | Mass: 8117.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02377 |
#27: Protein | Mass: 9399.887 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02371 |
#42: Protein | Mass: 17157.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: O97725 |
#43: Protein | Mass: 12737.620 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q05752 |
-NADH dehydrogenase [ubiquinone] 1 subunit ... , 2 types, 2 molecules cd
#28: Protein | Mass: 8796.211 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02376 |
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#29: Protein | Mass: 14159.332 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02827 |
-NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit ... , 11 types, 11 molecules fghijklmnop
#31: Protein | Mass: 6978.148 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02378 |
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#32: Protein | Mass: 17594.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q8HXG5 |
#33: Protein | Mass: 21624.135 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02380 |
#34: Protein | Mass: 15592.122 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02367 |
#35: Protein | Mass: 12298.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02374 |
#36: Protein | Mass: 11160.705 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02365 |
#37: Protein | Mass: 21678.459 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02372 |
#38: Protein | Mass: 15248.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P48305 |
#39: Protein | Mass: 21827.889 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02369 |
#40: Protein | Mass: 16428.846 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02368 |
#41: Protein | Mass: 21000.900 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: Q02373 |
-Non-polymers , 14 types, 37 molecules
#45: Chemical | ChemComp-3PE / #46: Chemical | ChemComp-PC1 / #47: Chemical | ChemComp-SF4 / #48: Chemical | #49: Chemical | ChemComp-FMN / | #50: Chemical | ChemComp-K / | #51: Chemical | ChemComp-CDL / #52: Chemical | ChemComp-DGT / | #53: Chemical | ChemComp-MG / | #54: Chemical | ChemComp-NDP / | #55: Chemical | ChemComp-ZN / | #56: Chemical | #57: Chemical | ChemComp-CHD / | #58: Chemical | ChemComp-MYR / | |
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-Details
Has ligand of interest | N |
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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: Complex I from Bos taurus reconstituted into proteoliposomes. Type: COMPLEX Details: Complex I from Bos taurus, purified as prepared in DDM, and reconstituted into proteoliposomes. Entity ID: #1-#44 / Source: NATURAL | |||||||||||||||
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Molecular weight | Value: 1.09 MDa / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Bos taurus (cattle) | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Complex I proteoliposomes on a graphene-oxide coated gold grid with even liposome distribution. | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K Details: Sample was incubated on grid for 30 s before plunge freezing |
-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 / Nominal magnification: 81000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 3.4 sec. / Electron dose: 39.9 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5568 Details: The data were collected with aberration-free image shift (AFIS). |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Width: 5760 / Height: 4092 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45661 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7QSO Accession code: 7QSO / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 93.6 Å2 | ||||||||||||||||||||||||||||||||||||||||
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