+Open data
-Basic information
Entry | Database: PDB / ID: 8om1 | |||||||||
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Title | Mitochondrial complex I from Mus musculus in the active state | |||||||||
Components |
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Keywords | OXIDOREDUCTASE / Mitochondrial complex I / Respiratory complex I / NADH:ubiquinone oxidoreductase | |||||||||
Function / homology | Function and homology information response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development ...response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching / respiratory system process / psychomotor behavior / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / response to light intensity / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / negative regulation of non-canonical NF-kappaB signal transduction / : / [2Fe-2S] cluster assembly / oxygen sensor activity / adult walking behavior / cellular response to glucocorticoid stimulus / ubiquinone-6 biosynthetic process / positive regulation of mitochondrial membrane potential / respiratory chain complex I / response to hydroperoxide / cellular respiration / iron-sulfur cluster assembly / NADH dehydrogenase activity / mitochondrial ribosome / adult behavior / dopamine metabolic process / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / acyl binding / ubiquinone binding / acyl carrier activity / cellular response to interferon-beta / neuron development / quinone binding / electron transport coupled proton transport / neurogenesis / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / muscle contraction / negative regulation of reactive oxygen species biosynthetic process / ATP metabolic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / mitochondrial ATP synthesis coupled electron transport / tricarboxylic acid cycle / mitochondrial respiratory chain complex I assembly / fatty acid metabolic process / : / visual perception / ionotropic glutamate receptor binding / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / cerebellum development / response to hormone / regulation of mitochondrial membrane potential / : / mitochondrion organization / mitochondrial electron transport, NADH to ubiquinone / response to cocaine / kidney development / synaptic membrane / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase (ubiquinone) activity / apoptotic signaling pathway / electron transport chain / sensory perception of sound / regulation of protein phosphorylation / response to nicotine / circadian rhythm / brain development / response to hydrogen peroxide / multicellular organism growth / mitochondrial membrane / response to organic cyclic compound / aerobic respiration / mitochondrial intermembrane space / negative regulation of cell growth / cognition / 2 iron, 2 sulfur cluster binding / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.39 Å | |||||||||
Authors | Grba, D.N. / Chung, I. / Bridges, H.R. / Agip, A.N.A. / Hirst, J. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Sci Adv / Year: 2023 Title: Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I. Authors: Daniel N Grba / Injae Chung / Hannah R Bridges / Ahmed-Noor A Agip / Judy Hirst / Abstract: Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the ...Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-Å resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8om1.cif.gz | 1.6 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8om1.ent.gz | 1.3 MB | Display | PDB format |
PDBx/mmJSON format | 8om1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8om1_validation.pdf.gz | 3.6 MB | Display | wwPDB validaton report |
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Full document | 8om1_full_validation.pdf.gz | 3.7 MB | Display | |
Data in XML | 8om1_validation.xml.gz | 228.6 KB | Display | |
Data in CIF | 8om1_validation.cif.gz | 362.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/om/8om1 ftp://data.pdbj.org/pub/pdb/validation_reports/om/8om1 | HTTPS FTP |
-Related structure data
Related structure data | 16965MC 8oltC M: map data used to model this data C: citing same article (ref.) |
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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: 13251.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03899, NADH:ubiquinone reductase (H+-translocating) |
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#8: Protein | Mass: 36105.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03888, NADH:ubiquinone reductase (H+-translocating) |
#10: Protein | Mass: 18656.100 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03925, NADH:ubiquinone reductase (H+-translocating) |
#11: Protein | Mass: 10637.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03903, NADH:ubiquinone reductase (H+-translocating) |
#12: Protein | Mass: 68547.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03921, NADH:ubiquinone reductase (H+-translocating) |
#13: Protein | Mass: 51943.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03911, NADH:ubiquinone reductase (H+-translocating) |
#14: Protein | Mass: 38800.230 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: P03893, NADH:ubiquinone reductase (H+-translocating) |
-NADH dehydrogenase [ubiquinone] iron-sulfur protein ... , 7 types, 7 molecules BCDIQRe
#2: Protein | Mass: 24730.904 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q9DC70, NADH:ubiquinone reductase (H+-translocating) |
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#3: Protein | Mass: 30191.307 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q9DCT2, NADH:ubiquinone reductase (H+-translocating) |
#4: Protein | Mass: 52720.602 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q91WD5, NADH:ubiquinone reductase (H+-translocating) |
#9: Protein | Mass: 24068.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q8K3J1, NADH:ubiquinone reductase (H+-translocating) |
#17: Protein | Mass: 19814.725 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CXZ1 |
#18: Protein | Mass: 13041.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: P52503 |
#30: Protein | Mass: 12675.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q99LY9 |
-NADH dehydrogenase [ubiquinone] flavoprotein ... , 3 types, 3 molecules EFs
#5: Protein | Mass: 27318.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q9D6J6, NADH:ubiquinone reductase (H+-translocating) |
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#6: Protein | Mass: 50904.152 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q91YT0, NADH:ubiquinone reductase (H+-translocating) |
#44: Protein | Mass: 11833.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q8BK30 |
-Protein , 2 types, 3 molecules GTU
#7: Protein | Mass: 79866.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart References: UniProt: Q91VD9, NADH:ubiquinone reductase (H+-translocating) |
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#20: Protein | Mass: 17390.289 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CR21 |
-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 12 types, 12 molecules OPSVWXYZabqr
#15: Protein | Mass: 40657.375 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q99LC3 |
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#16: Protein | Mass: 42588.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9DC69 |
#19: Protein | Mass: 10932.675 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQ75 |
#21: Protein | Mass: 13380.719 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CPP6 |
#22: Protein | Mass: 15311.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQZ5 |
#23: Protein | Mass: 20025.127 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9DCJ5 |
#24: Protein | Mass: 14999.220 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: G5E814 |
#25: Protein | Mass: 16881.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9ERS2 |
#26: Protein | Mass: 8149.524 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: O35683 |
#27: Protein | Mass: 9338.867 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQ91 |
#42: Protein | Mass: 17154.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q7TMF3 |
#43: Protein | Mass: 12506.432 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9Z1P6 |
-NADH dehydrogenase [ubiquinone] 1 subunit ... , 2 types, 2 molecules cd
#28: Protein | Mass: 8636.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQY9 |
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#29: Protein | Mass: 14185.692 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQ54 |
-NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit ... , 11 types, 11 molecules fghijklmnop
#31: Protein | Mass: 6965.109 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: P0DN34 |
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#32: Protein | Mass: 17463.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: O09111 |
#33: Protein | Mass: 21742.197 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQH3 |
#34: Protein | Mass: 15450.925 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q3UIU2 |
#35: Protein | Mass: 11982.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CPU2 |
#36: Protein | Mass: 11714.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQZ6 |
#37: Protein | Mass: 21903.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9D6J5 |
#38: Protein | Mass: 15105.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQC7 |
#39: Protein | Mass: 22020.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Tissue: Heart / References: UniProt: Q9CQJ8 |
#40: Protein | Mass: 16229.606 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CR61 |
#41: Protein | Mass: 21054.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9DCS9 |
-Sugars , 1 types, 16 molecules
#45: Sugar | ChemComp-LMT / |
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-Non-polymers , 14 types, 2989 molecules
#46: Chemical | ChemComp-PC1 / #47: Chemical | ChemComp-SF4 / #48: Chemical | #49: Chemical | ChemComp-FMN / | #50: Chemical | ChemComp-NA / | #51: Chemical | ChemComp-CDL / #52: Chemical | ChemComp-3PE / #53: Chemical | ChemComp-MG / | #54: Chemical | ChemComp-DGT / | #55: Chemical | ChemComp-NDP / | #56: Chemical | ChemComp-ZN / | #57: Chemical | #58: Chemical | ChemComp-MYR / | #59: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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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: Mitochondrial respiratory complex I / Type: COMPLEX Details: Native purification of mitochondrial complex I from mouse hearts Entity ID: #1, #3-#39, #42-#44 / Source: NATURAL | ||||||||||||||||||||
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Molecular weight | Value: 1 MDa / Experimental value: YES | ||||||||||||||||||||
Source (natural) | Organism: Mus musculus (house mouse) / Organ: Heart | ||||||||||||||||||||
Buffer solution | pH: 7.14 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Details: Following glow discharge for 90 s at 20 mA, the grid was treated for 48 hours in an anaerobic glovebox in ethanol containing 5 mM 11-mercaptoundecyl hexaethyleneglycol, washed three times in ...Details: Following glow discharge for 90 s at 20 mA, the grid was treated for 48 hours in an anaerobic glovebox in ethanol containing 5 mM 11-mercaptoundecyl hexaethyleneglycol, washed three times in ethanol and dried prior to blotting Grid material: GOLD / Grid type: UltrAuFoil | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: blot for 10 seconds before plunging |
-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: 2000 nm / Nominal defocus min: 800 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: 2.53 sec. / Electron dose: 39.94 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2674 |
-Processing
Software | Name: UCSF ChimeraX / Version: 1.5/v9 / Classification: model building / URL: https://www.rbvi.ucsf.edu/chimerax/ / Os: macOS / Type: package | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 357798 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.39 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 109866 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6ZR2 Accession code: 6ZR2 / Source name: PDB / Type: experimental model |