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Yorodumi- PDB-8olt: Mitochondrial complex I from Mus musculus in the active state bou... -
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-Basic information
Entry | Database: PDB / ID: 8olt | |||||||||
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Title | Mitochondrial complex I from Mus musculus in the active state bound with piericidin A | |||||||||
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 / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / blastocyst hatching / circulatory system development ...response to injury involved in regulation of muscle adaptation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / blastocyst hatching / circulatory system development / response to light intensity / respiratory system process / protein insertion into mitochondrial inner membrane / psychomotor behavior / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / : / [2Fe-2S] cluster assembly / oxygen sensor activity / adult walking behavior / respiratory chain complex I / cellular response to glucocorticoid stimulus / deoxynucleoside kinase activity / negative regulation of non-canonical NF-kappaB signal transduction / positive regulation of mitochondrial membrane potential / response to hydroperoxide / cellular respiration / ubiquinone-6 biosynthetic process / iron-sulfur cluster assembly / 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 / NADH dehydrogenase activity / apoptotic mitochondrial changes / mitochondrial ATP synthesis coupled electron transport / : / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / ubiquinone binding / mitochondrial respiratory chain complex I assembly / NADH dehydrogenase (ubiquinone) activity / acyl binding / neuron development / cellular response to interferon-beta / acyl carrier activity / quinone binding / electron transport coupled proton transport / ATP synthesis coupled electron transport / negative regulation of reactive oxygen species biosynthetic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / ATP metabolic process / tricarboxylic acid cycle / response to organonitrogen compound / visual perception / aerobic respiration / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / mitochondrion organization / cerebellum development / neurogenesis / regulation of mitochondrial membrane potential / response to hormone / response to cocaine / fatty acid metabolic process / synaptic membrane / kidney development / muscle contraction / mitochondrial membrane / apoptotic signaling pathway / electron transport chain / sensory perception of sound / regulation of protein phosphorylation / ionotropic glutamate receptor binding / response to nicotine / response to hydrogen peroxide / multicellular organism growth / response to organic cyclic compound / mitochondrial intermembrane space / brain development / negative regulation of cell growth / cognition / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.84 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 | 8olt.cif.gz | 1.5 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8olt.ent.gz | 1.2 MB | Display | PDB format |
PDBx/mmJSON format | 8olt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8olt_validation.pdf.gz | 3.5 MB | Display | wwPDB validaton report |
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Full document | 8olt_full_validation.pdf.gz | 3.7 MB | Display | |
Data in XML | 8olt_validation.xml.gz | 228.1 KB | Display | |
Data in CIF | 8olt_validation.cif.gz | 337.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/8olt ftp://data.pdbj.org/pub/pdb/validation_reports/ol/8olt | HTTPS FTP |
-Related structure data
Related structure data | 16962MC 8om1C 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) 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) 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) 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) 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) 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) 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) References: UniProt: P03893, NADH:ubiquinone reductase (H+-translocating) |
-NADH dehydrogenase [ubiquinone] iron-sulfur protein ... , 7 types, 7 molecules BCDIQRe
#2: Protein | Mass: 24715.912 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) 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) 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) 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) 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) / 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) / 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) / 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) 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) 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) / 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) 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) / 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) / 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) / 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) / 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) / 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) / 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) / References: UniProt: Q9DCJ5 |
#24: Protein | Mass: 15130.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / 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) / 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) / 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) / 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) / References: UniProt: Q7TMF3 |
#43: Protein | Mass: 12637.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / 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) / 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) / 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) / 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) / 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) / References: UniProt: Q9CQH3 |
#34: Protein | Mass: 15582.122 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / 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) / 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) / 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) / 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) / 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) / References: UniProt: Q9CQJ8 |
#40: Protein | Mass: 16360.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: NADH:ubiquinone reductase (H+-translocating) |
#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 , 15 types, 320 molecules
#46: Chemical | #47: Chemical | ChemComp-SF4 / #48: Chemical | ChemComp-HQH / | #49: Chemical | #50: Chemical | ChemComp-FMN / | #51: Chemical | ChemComp-NA / | #52: Chemical | ChemComp-CDL / #53: Chemical | ChemComp-3PE / #54: Chemical | ChemComp-MG / | #55: Chemical | ChemComp-GTP / | #56: Chemical | ChemComp-NDP / | #57: Chemical | ChemComp-ZN / | #58: Chemical | #59: Chemical | ChemComp-MYR / | #60: 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-#39, #41-#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 / Details: PH corrected at room temperature | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 4.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Details: The grid was treated for 48 hours in an anaerobic glovebox in ethanol containing 5mM 11-mercaptoundecylhexaethyleneglycol, washed three times in ethanol and air dried prior to use. Note the ...Details: The grid was treated for 48 hours in an anaerobic glovebox in ethanol containing 5mM 11-mercaptoundecylhexaethyleneglycol, washed three times in ethanol and air dried prior to use. Note the hole sizes are R0.6/1. Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: blot for 10 to 12 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: 47600 X / Nominal defocus max: 3400 nm / Nominal defocus min: 2200 nm / Cs: 2.7 mm | |||||||||||||||||||||
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER | |||||||||||||||||||||
Image recording | Imaging-ID: 1 / Detector mode: COUNTING / Num. of grids imaged: 1
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EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV | |||||||||||||||||||||
Image scans |
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-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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Image processing | Details: The final reconstruction is combined from two branches with one coming from a K2 detector and the other from a Falcon III. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 63952 Details: This is from an initial of 36,759 and 27,193 particles from the Falcon III and K2 detectors, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.84 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 41670 Details: This is the combined particles from the two branches of data collected on the two different detectors Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6ZR2 Accession code: 6ZR2 / Source name: PDB / Type: experimental model |