[English] 日本語
Yorodumi- EMDB-11425: Cryo-EM structure of respiratory complex I from Mus musculus inhi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11425 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of respiratory complex I from Mus musculus inhibited by piericidin A at 3.0 A (Falcon 3) | ||||||||||||
Map data | |||||||||||||
Sample |
| ||||||||||||
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 / respiratory system process / protein insertion into mitochondrial inner membrane ...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 / respiratory system process / protein insertion into mitochondrial inner membrane / response to light intensity / blastocyst hatching / circulatory system development / ubiquinone-6 biosynthetic process / cellular response to oxygen levels / iron-sulfur cluster assembly complex / psychomotor behavior / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / [2Fe-2S] cluster assembly / mitochondrial respirasome / cardiac muscle tissue development / NADH dehydrogenase activity / oxygen sensor activity / cellular respiration / respiratory chain complex I / adult walking behavior / negative regulation of non-canonical NF-kappaB signal transduction / ubiquinone binding / cellular response to glucocorticoid stimulus / acyl binding / response to hydroperoxide / : / mitochondrial ribosome / electron transport coupled proton transport / positive regulation of mitochondrial membrane potential / iron-sulfur cluster assembly / mitochondrial ATP synthesis coupled electron transport / acyl carrier activity / mitochondrial translation / adult behavior / dopamine metabolic process / NADH:ubiquinone reductase (H+-translocating) / positive regulation of ATP biosynthetic process / proton motive force-driven mitochondrial ATP synthesis / mitochondrial respiratory chain complex I / apoptotic mitochondrial changes / neuron development / mitochondrial respiratory chain complex I assembly / mitochondrial electron transport, NADH to ubiquinone / electron transport chain / NADH dehydrogenase (ubiquinone) activity / quinone binding / ATP synthesis coupled electron transport / cellular response to interferon-beta / negative regulation of intrinsic apoptotic signaling pathway / aerobic respiration / ATP metabolic process / negative regulation of reactive oxygen species biosynthetic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / response to cAMP / tricarboxylic acid cycle / response to organonitrogen compound / ionotropic glutamate receptor binding / visual perception / reactive oxygen species metabolic process / Neutrophil degranulation / cerebellum development / respiratory electron transport chain / neurogenesis / response to hormone / kidney development / response to cocaine / fatty acid metabolic process / regulation of mitochondrial membrane potential / response to nicotine / muscle contraction / synaptic membrane / apoptotic signaling pathway / mitochondrial membrane / multicellular organism growth / sensory perception of sound / regulation of protein phosphorylation / brain development / response to hydrogen peroxide / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / cognition / response to organic cyclic compound / negative regulation of cell growth / circadian rhythm / positive regulation of protein catabolic process / NAD binding / positive regulation of fibroblast proliferation / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding 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
| ||||||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
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 | |
---|---|---|---|---|
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 |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
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) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.063 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Mask #1
File | emd_11425_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_11425_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_11425_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Respiratory complex I
Entire | Name: Respiratory complex I |
---|---|
Components |
|
-Supramolecule #1: Respiratory complex I
Supramolecule | Name: Respiratory complex I / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#45 |
---|---|
Source (natural) | Organism: Mus musculus (house mouse) / Strain: C57BL/6 / Organ: heart |
Molecular weight | Theoretical: 980 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.1 mg/mL | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / 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 |
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 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |