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Yorodumi- EMDB-11811: Cryo-EM structure of ND6-P25L mutant respiratory complex I from M... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11811 | |||||||||
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Title | Cryo-EM structure of ND6-P25L mutant respiratory complex I from Mus musculus at 3.8 A | |||||||||
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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 / 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 / respirasome / 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 Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) / Mouse (mice) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.82 Å | |||||||||
Authors | Yin Z / Bridges HR / Grba D / Hirst J | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Nat Commun / Year: 2021 Title: Structural basis for a complex I mutation that blocks pathological ROS production. Authors: Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / ...Authors: Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / Michael P Murphy / Judy Hirst / Abstract: Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease- ...Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury. | |||||||||
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_11811.map.gz | 322.7 MB | EMDB map data format | |
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Header (meta data) | emd-11811-v30.xml emd-11811.xml | 65.1 KB 65.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11811_fsc.xml | 16 KB | Display | FSC data file |
Images | emd_11811.png | 61.1 KB | ||
Masks | emd_11811_msk_1.map | 347.6 MB | Mask map | |
Others | emd_11811_half_map_1.map.gz emd_11811_half_map_2.map.gz | 277.8 MB 277.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11811 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11811 | HTTPS FTP |
-Related structure data
Related structure data | 7ak6MC 7ak5C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10605 (Title: Single particle cryo-EM dataset of Mus musculus mitochondrial complex I with ND6 P25L mutation Data size: 3.1 TB Data #1: Single particle cryo-EM dataset of Mus musculus mitochondrial complex I with ND6 P25L mutation [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_11811.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: 1.054 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_11811_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_11811_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_11811_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Mouse mitochondrial complex I with ND6-P25L mutation
+Supramolecule #1: Mouse mitochondrial complex I with ND6-P25L mutation
+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 | 3.5 mg/mL |
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Buffer | pH: 7.14 |
Grid | Model: Quantifoil R0.6/1 / Material: GOLD / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal magnification: 130000 |
Specialist optics | Energy filter - Slit width: 20 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Details | Preliminary grid screening was performed manually. |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.015 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |