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Yorodumi- PDB-6zr2: Cryo-EM structure of respiratory complex I in the active state fr... -
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Basic information
| Entry | Database: PDB / ID: 6zr2 | |||||||||||||||||||||||||||||||||||||||||||||
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| Title | Cryo-EM structure of respiratory complex I in the active state from Mus musculus at 3.1 A | |||||||||||||||||||||||||||||||||||||||||||||
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Keywords | OXIDOREDUCTASE / NADH / ubiquinone / complex I | |||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationMitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / blastocyst hatching / sperm glycocalyx / perinuclear theca / psychomotor behavior / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation ...Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / blastocyst hatching / sperm glycocalyx / perinuclear theca / psychomotor behavior / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Mitochondrial ribosome-associated quality control / circulatory system development / Mitochondrial translation termination / Respiratory electron transport / mesenchymal stem cell differentiation / protein insertion into mitochondrial inner membrane / response to light intensity / respiratory system process / sperm head-tail coupling apparatus / adult walking behavior / Mitochondrial protein degradation / stem cell division / mitochondrial large ribosomal subunit assembly / mitochondrial ATP synthesis coupled electron transport / protein lipoylation / cellular response to oxygen levels / adult behavior / neural precursor cell proliferation / mitochondrial [2Fe-2S] assembly complex / mitochondrial large ribosomal subunit binding / ubiquinone biosynthetic process / respiratory chain complex / gliogenesis / negative regulation of non-canonical NF-kappaB signal transduction / cellular respiration / response to hydroperoxide / cardiac muscle tissue development / oxidative phosphorylation / positive regulation of mitochondrial membrane potential / [2Fe-2S] cluster assembly / oxygen sensor activity / sperm principal piece / cellular response to glucocorticoid stimulus / multicellular organism growth / iron-sulfur cluster assembly / dopamine metabolic process / sperm end piece / NADH:ubiquinone reductase (H+-translocating) / ubiquinone binding / mitochondrial electron transport, NADH to ubiquinone / positive regulation of ATP biosynthetic process / proton motive force-driven mitochondrial ATP synthesis / neuron development / electron transport coupled proton transport / acyl binding / regulation of protein phosphorylation / mitochondrial respiratory chain complex I assembly / oxidoreductase activity, acting on NAD(P)H / NADH dehydrogenase activity / reactive oxygen species metabolic process / cerebellum development / respiratory chain complex I / positive regulation of execution phase of apoptosis / response to cAMP / NADH dehydrogenase (ubiquinone) activity / acyl carrier activity / neuron apoptotic process / extrinsic apoptotic signaling pathway / cellular response to interferon-beta / neurogenesis / quinone binding / cellular response to retinoic acid / ATP synthesis coupled electron transport / negative regulation of reactive oxygen species biosynthetic process / kidney development / visual perception / sensory perception of sound / Neutrophil degranulation / response to hormone / in utero embryonic development / muscle contraction / gene expression / fatty acid metabolic process / ionotropic glutamate receptor binding / acrosomal vesicle / regulation of mitochondrial membrane potential / sperm midpiece / DNA damage response, signal transduction by p53 class mediator / aerobic respiration / mitochondrion organization / response to hydrogen peroxide / synaptic membrane / brain development / response to nicotine / response to cocaine / respiratory electron transport chain / monooxygenase activity / myelin sheath Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||
| Biological species | ![]() | |||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||||||||||||||||||||||||||||||||
Authors | Bridges, H.R. / Blaza, J.N. / Agip, A.N.A. / Hirst, J. | |||||||||||||||||||||||||||||||||||||||||||||
| Funding support | United Kingdom, 3items
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Citation | Journal: Nat Commun / Year: 2020Title: Structure of inhibitor-bound mammalian complex I. Authors: Hannah R Bridges / Justin G Fedor / James N Blaza / Andrea Di Luca / Alexander Jussupow / Owen D Jarman / John J Wright / Ahmed-Noor A Agip / Ana P Gamiz-Hernandez / Maxie M Roessler / Ville ...Authors: Hannah R Bridges / Justin G Fedor / James N Blaza / Andrea Di Luca / Alexander Jussupow / Owen D Jarman / John J Wright / Ahmed-Noor A Agip / Ana P Gamiz-Hernandez / Maxie M Roessler / Ville R I Kaila / Judy Hirst / ![]() Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power ...Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I. | |||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 6zr2.cif.gz | 1.5 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb6zr2.ent.gz | 1.2 MB | Display | PDB format |
| PDBx/mmJSON format | 6zr2.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zr/6zr2 ftp://data.pdbj.org/pub/pdb/validation_reports/zr/6zr2 | HTTPS FTP |
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-Related structure data
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Links
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Assembly
| Deposited unit | ![]()
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Components
-NADH-ubiquinone oxidoreductase chain ... , 7 types, 7 molecules AHJKLMN
| #1: Protein | Mass: 13251.785 Da / Num. of mol.: 1 / Mutation: N-terminal Formylation / Source method: isolated from a natural source / Source: (natural) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() 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) ![]() |
| #18: Protein | Mass: 13041.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #30: Protein | Mass: 12675.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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) ![]() 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) ![]() 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) ![]() |
-Protein , 3 types, 4 molecules GTUY
| #7: Protein | Mass: 79866.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() 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) ![]() #24: Protein | | Mass: 15130.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 Source: (natural) ![]() |
-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 11 types, 11 molecules OPSVWXZabqr
| #15: Protein | Mass: 40657.375 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #16: Protein | Mass: 42588.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #19: Protein | Mass: 10932.675 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #21: Protein | Mass: 13380.719 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #22: Protein | Mass: 15311.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #23: Protein | Mass: 20025.127 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #25: Protein | Mass: 16881.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #26: Protein | Mass: 8149.524 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #27: Protein | Mass: 9338.867 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #42: Protein | Mass: 17154.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #43: Protein | Mass: 12637.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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) ![]() |
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| #29: Protein | Mass: 14185.692 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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) ![]() |
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| #32: Protein | Mass: 17463.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #33: Protein | Mass: 21742.197 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #34: Protein | Mass: 15582.122 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #35: Protein | Mass: 11982.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #36: Protein | Mass: 11714.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #37: Protein | Mass: 21903.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #38: Protein | Mass: 15105.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #39: Protein | Mass: 22020.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #40: Protein | Mass: 16360.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #41: Protein | Mass: 21054.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 10 types, 34 molecules 


















| #45: Chemical | ChemComp-SF4 / #46: Chemical | ChemComp-PC1 / #47: Chemical | #48: Chemical | ChemComp-FMN / | #49: Chemical | ChemComp-3PE / #50: Chemical | ChemComp-CDL / #51: Chemical | ChemComp-ATP / | #52: Chemical | ChemComp-NDP / | #53: Chemical | ChemComp-ZN / | #54: Chemical | |
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-Details
| Has ligand of interest | N |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Respiratory complex I / Type: COMPLEX / Entity ID: #1-#44 / Source: NATURAL | ||||||||||||||||||||
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| Molecular weight | Value: 0.98 MDa / Experimental value: NO | ||||||||||||||||||||
| Source (natural) | Organism: ![]() | ||||||||||||||||||||
| Buffer solution | pH: 7.14 / Details: pH corrected at room temperature | ||||||||||||||||||||
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| Specimen | Conc.: 3 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 5 mM 11-mercaptoundecylhexaethyleneglycol, washed in ethanol three times and air dried prior to use. Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R0.6/1 | ||||||||||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Details: blot for 10 seconds before plunging |
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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: 3100 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 |
| Image scans | Width: 3838 / Height: 3710 / Movie frames/image: 24 / Used frames/image: 1-12 |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
| 3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 20370 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||
| Atomic model building | Protocol: OTHER / Space: REAL | |||||||||||||||
| Refinement | Highest resolution: 3.1 Å |
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United Kingdom, 3items
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