[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 / Protein lipoylation / reproductive system development / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / circulatory system development ...response to injury involved in regulation of muscle adaptation / Protein lipoylation / reproductive system development / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching / respiratory system process / psychomotor behavior / Mitochondrial protein degradation / response to light intensity / cellular response to oxygen levels / iron-sulfur cluster assembly complex / ubiquinone-6 biosynthetic process / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / : / negative regulation of non-canonical NF-kappaB signal transduction / [2Fe-2S] cluster assembly / adult walking behavior / oxygen sensor activity / cellular response to glucocorticoid stimulus / response to hydroperoxide / positive regulation of mitochondrial membrane potential / cellular respiration / respiratory chain complex I / iron-sulfur cluster assembly / mitochondrial ribosome / adult behavior / mitochondrial translation / positive regulation of ATP biosynthetic process / dopamine metabolic process / positive regulation of execution phase of apoptosis / NADH:ubiquinone reductase (H+-translocating) / : / ubiquinone binding / NADH dehydrogenase activity / apoptotic mitochondrial changes / : / mitochondrial ATP synthesis coupled electron transport / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / proton motive force-driven mitochondrial ATP synthesis / electron transport coupled proton transport / acyl binding / cellular response to interferon-beta / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / neuron development / quinone binding / ATP synthesis coupled electron transport / cellular response to retinoic acid / negative regulation of intrinsic apoptotic signaling pathway / muscle contraction / negative regulation of reactive oxygen species biosynthetic process / ATP metabolic process / extrinsic apoptotic signaling pathway / tricarboxylic acid cycle / visual perception / aerobic respiration / ionotropic glutamate receptor binding / response to hormone / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / neurogenesis / cerebellum development / regulation of mitochondrial membrane potential / kidney development / mitochondrion organization / response to cocaine / fatty acid metabolic process / cognition / synaptic membrane / mitochondrial membrane / apoptotic signaling pathway / sensory perception of sound / electron transport chain / response to nicotine / regulation of protein phosphorylation / response to hydrogen peroxide / multicellular organism growth / brain development / response to organic cyclic compound / negative regulation of cell growth / mitochondrial intermembrane space / 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 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 |
-Validation report
Summary document | emd_11425_validation.pdf.gz | 465.1 KB | Display | EMDB validaton report |
---|---|---|---|---|
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 |
---|---|
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) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
---|---|
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 |