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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-14127 | |||||||||
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Title | Bovine complex I in the active state at 3.1 A | |||||||||
![]() | Consensus map locally sharpened | |||||||||
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Function / homology | ![]() Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / ubiquinone biosynthetic process / Respiratory electron transport / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / [2Fe-2S] cluster assembly ...Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / ubiquinone biosynthetic process / Respiratory electron transport / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / [2Fe-2S] cluster assembly / oxygen sensor activity / Neutrophil degranulation / mitochondrial ATP synthesis coupled electron transport / Mitochondrial protein degradation / acyl binding / ubiquinone binding / acyl carrier activity / electron transport coupled proton transport / NADH:ubiquinone reductase (H+-translocating) / mitochondrial respiratory chain complex I assembly / mitochondrial electron transport, NADH to ubiquinone / NADH dehydrogenase activity / respiratory chain complex I / NADH dehydrogenase (ubiquinone) activity / quinone binding / ATP synthesis coupled electron transport / response to cAMP / neurogenesis / reactive oxygen species metabolic process / aerobic respiration / fatty acid binding / respiratory electron transport chain / electron transport chain / mitochondrial membrane / brain development / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / circadian rhythm / NAD binding / fatty acid biosynthetic process / FMN binding / 4 iron, 4 sulfur cluster binding / mitochondrial inner membrane / oxidoreductase activity / mitochondrial matrix / negative regulation of DNA-templated transcription / apoptotic process / protein-containing complex binding / mitochondrion / nucleoplasm / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Bridges HR / Blaza JN / Yin Z / Chung I / Hirst J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides. Authors: Hannah R Bridges / James N Blaza / Zhan Yin / Injae Chung / Michael N Pollak / Judy Hirst / ![]() ![]() Abstract: The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target ...The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides. #1: ![]() Title: Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy Authors: Chung I / Wright JJ / Bridges HR / Ivanov BS / Biner O / Pereira CS / Arantes GM / Hirst J | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 324.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 68.2 KB 68.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 15.9 KB | Display | ![]() |
Images | ![]() | 90.3 KB | ||
Masks | ![]() | 347.6 MB | ![]() | |
Others | ![]() ![]() ![]() | 325.8 MB 280 MB 279.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7qsdMC ![]() 7r41C ![]() 7r42C ![]() 7r43C ![]() 7r44C ![]() 7r45C ![]() 7r46C ![]() 7r47C ![]() 7r48C ![]() 7r4cC ![]() 7r4dC ![]() 7r4fC ![]() 7r4gC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Consensus map locally sharpened | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.056 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Density Histograms |
-Additional map: Consensus map globally sharpened
File | emd_14127_additional_1.map | ||||||||||||
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Annotation | Consensus map globally sharpened | ||||||||||||
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Density Histograms |
-Half map: Consensus halfmap1
File | emd_14127_half_map_1.map | ||||||||||||
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Annotation | Consensus halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Consensus halfmap2
File | emd_14127_half_map_2.map | ||||||||||||
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Annotation | Consensus halfmap2 | ||||||||||||
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Density Histograms |
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Sample components
+Entire : NADH Ubiquinone oxidoreductase (Complex I)
+Supramolecule #1: NADH Ubiquinone oxidoreductase (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: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11
+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: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #46: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+Macromolecule #47: IRON/SULFUR CLUSTER
+Macromolecule #48: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #49: FLAVIN MONONUCLEOTIDE
+Macromolecule #50: CARDIOLIPIN
+Macromolecule #51: DODECYL-BETA-D-MALTOSIDE
+Macromolecule #52: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #53: MAGNESIUM ION
+Macromolecule #54: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #55: ZINC ION
+Macromolecule #56: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3 mg/mL | ||||||||||||
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Buffer | pH: 7.14 Component:
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Grid | Model: UltrAuFoil R0.6/1 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 90 sec. / Pretreatment - Atmosphere: AIR Details: Grid also covalently modified by peg-thiol in a nitrogen atmosphere for 48 hours. | ||||||||||||
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |