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Yorodumi- EMDB-11425: Cryo-EM structure of respiratory complex I from Mus musculus inhi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11425 | ||||||||||||
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Title | Cryo-EM structure of respiratory complex I from Mus musculus inhibited by piericidin A at 3.0 A (Falcon 3) | ||||||||||||
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Sample |
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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 / circulatory system development / blastocyst hatching ...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 / circulatory system development / blastocyst hatching / response to light intensity / protein insertion into mitochondrial inner membrane / respiratory system process / 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 / deoxynucleoside kinase activity / negative regulation of non-canonical NF-kappaB signal transduction / cellular response to glucocorticoid stimulus / positive regulation of mitochondrial membrane potential / response to hydroperoxide / respiratory chain complex I / cellular respiration / ubiquinone-6 biosynthetic process / 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 / mitochondrial ATP synthesis coupled electron transport / : / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / mitochondrial respiratory chain complex I assembly / ubiquinone binding / acyl binding / NADH dehydrogenase (ubiquinone) activity / 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 / negative regulation of intrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway / ATP metabolic process / cellular response to retinoic acid / tricarboxylic acid cycle / : / muscle contraction / visual perception / aerobic respiration / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / cerebellum development / neurogenesis / mitochondrion organization / response to hormone / regulation of mitochondrial membrane potential / fatty acid metabolic process / response to cocaine / kidney development / synaptic membrane / 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 / mitochondrial intermembrane space / response to organic cyclic compound / 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 | single particle reconstruction / cryo EM / Resolution: 3.0 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_11425.map.gz | 325.6 MB | EMDB map data format | |
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Header (meta data) | emd-11425-v30.xml emd-11425.xml | 23.2 KB 23.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11425_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_11425.png | 53.8 KB | ||
Masks | emd_11425_msk_1.map | 347.6 MB | Mask map | |
Others | emd_11425_half_map_1.map.gz emd_11425_half_map_2.map.gz | 279.2 MB 279 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11425 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11425 | HTTPS FTP |
-Validation report
Summary document | emd_11425_validation.pdf.gz | 465.1 KB | Display | EMDB validaton report |
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Full document | emd_11425_full_validation.pdf.gz | 464.2 KB | Display | |
Data in XML | emd_11425_validation.xml.gz | 21.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11425 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11425 | 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_11425.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.063 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_11425_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_11425_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_11425_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : Respiratory complex I
Entire | Name: Respiratory complex I |
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Components |
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-Supramolecule #1: Respiratory complex I
Supramolecule | Name: Respiratory complex I / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#45 |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: C57BL/6 / Organ: heart |
Molecular weight | Theoretical: 980 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.1 mg/mL | ||||||||||||
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Buffer | pH: 7.14 Component:
Details: pH corrected at room temperature | ||||||||||||
Grid | Model: UltrAuFoil R0.6/1 / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: OTHER Details: the grid was treated for 48 hours in an anaerobic glovebox in ethanol containing 5mM 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: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Frames/image: 1-12 / Number grids imaged: 1 / Average electron dose: 46.0 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: 3.8 µm / Nominal defocus min: 2.2 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |