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Yorodumi- EMDB-11377: Cryo-EM structure of respiratory complex I in the active state fr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11377 | ||||||||||||
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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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Sample |
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Function / homology | Function and homology information Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching ...Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / circulatory system development / respiratory system process / psychomotor behavior / ubiquinone-6 biosynthetic process / Mitochondrial protein degradation / response to light intensity / cellular response to oxygen levels / iron-sulfur cluster assembly complex / : / mitochondrial large ribosomal subunit binding / gliogenesis / negative regulation of non-canonical NF-kappaB signal transduction / cellular response to glucocorticoid stimulus / neural precursor cell proliferation / cardiac muscle tissue development / [2Fe-2S] cluster assembly / oxygen sensor activity / adult walking behavior / positive regulation of mitochondrial membrane potential / response to hydroperoxide / : / ubiquinone binding / iron-sulfur cluster assembly / positive regulation of ATP biosynthetic process / adult behavior / dopamine metabolic process / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / proton motive force-driven mitochondrial ATP synthesis / 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 / neuron development / acyl binding / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / cellular response to interferon-beta / negative regulation of intrinsic apoptotic signaling pathway / ATP synthesis coupled electron transport / quinone binding / cellular response to retinoic acid / negative regulation of reactive oxygen species biosynthetic process / muscle contraction / extrinsic apoptotic signaling pathway / ionotropic glutamate receptor binding / tricarboxylic acid cycle / Neutrophil degranulation / aerobic respiration / visual perception / response to hormone / neurogenesis / respiratory electron transport chain / cerebellum development / reactive oxygen species metabolic process / kidney development / regulation of mitochondrial membrane potential / response to cocaine / synaptic membrane / mitochondrion organization / fatty acid metabolic process / response to nicotine / mitochondrial membrane / sensory perception of sound / electron transport chain / brain development / regulation of protein phosphorylation / response to hydrogen peroxide / negative regulation of cell growth / multicellular organism growth / response to organic cyclic compound / mitochondrial intermembrane space / cognition / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding / protease binding / in utero embryonic development / neuron apoptotic process / response to ethanol / response to oxidative stress Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) / Mouse (mice) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||
Authors | Bridges HR / Blaza JN / Agip ANA / Hirst J | ||||||||||||
Funding support | United Kingdom, 3 items
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Citation | Journal: Nat Commun / Year: 2020 Title: 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. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_11377.map.gz | 326.1 MB | EMDB map data format | |
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Header (meta data) | emd-11377-v30.xml emd-11377.xml | 65.6 KB 65.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11377_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_11377.png | 53.4 KB | ||
Masks | emd_11377_msk_1.map | 347.6 MB | Mask map | |
Others | emd_11377_half_map_1.map.gz emd_11377_half_map_2.map.gz | 278.1 MB 277.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11377 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11377 | HTTPS FTP |
-Validation report
Summary document | emd_11377_validation.pdf.gz | 487.4 KB | Display | EMDB validaton report |
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Full document | emd_11377_full_validation.pdf.gz | 486.5 KB | Display | |
Data in XML | emd_11377_validation.xml.gz | 21.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11377 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11377 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_11377.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.054 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_11377_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_11377_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_11377_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Respiratory complex I
+Supramolecule #1: Respiratory complex I
+Macromolecule #1: NADH-ubiquinone oxidoreductase chain 3
+Macromolecule #2: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+Macromolecule #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+Macromolecule #4: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+Macromolecule #5: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+Macromolecule #6: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+Macromolecule #7: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
+Macromolecule #8: NADH-ubiquinone oxidoreductase chain 1
+Macromolecule #9: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+Macromolecule #10: NADH-ubiquinone oxidoreductase chain 6
+Macromolecule #11: NADH-ubiquinone oxidoreductase chain 4L
+Macromolecule #12: NADH-ubiquinone oxidoreductase chain 5
+Macromolecule #13: NADH-ubiquinone oxidoreductase chain 4
+Macromolecule #14: NADH-ubiquinone oxidoreductase chain 2
+Macromolecule #15: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mi...
+Macromolecule #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+Macromolecule #17: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
+Macromolecule #18: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
+Macromolecule #19: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+Macromolecule #20: Acyl carrier protein, mitochondrial
+Macromolecule #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+Macromolecule #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+Macromolecule #23: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+Macromolecule #24: MCG5603
+Macromolecule #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+Macromolecule #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+Macromolecule #27: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+Macromolecule #28: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+Macromolecule #29: NADH dehydrogenase [ubiquinone] 1 subunit C2
+Macromolecule #30: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+Macromolecule #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+Macromolecule #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+Macromolecule #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+Macromolecule #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+Macromolecule #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+Macromolecule #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+Macromolecule #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+Macromolecule #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+Macromolecule #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+Macromolecule #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+Macromolecule #41: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+Macromolecule #42: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12
+Macromolecule #43: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+Macromolecule #44: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+Macromolecule #45: IRON/SULFUR CLUSTER
+Macromolecule #46: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #47: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #48: FLAVIN MONONUCLEOTIDE
+Macromolecule #49: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE
+Macromolecule #50: CARDIOLIPIN
+Macromolecule #51: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #52: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #53: ZINC ION
+Macromolecule #54: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3 mg/mL | ||||||||||||
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Buffer | pH: 7.14 Component:
Details: pH corrected at room temperature | ||||||||||||
Grid | Model: UltrAuFoil R0.6/1 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR 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. | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV / Details: blot for 10 seconds before plunging. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 1-12 / Number grids imaged: 1 / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.1 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 47600 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |