[English] 日本語
![](img/lk-miru.gif)
- EMDB-16518: Cryo-EM structure NDUFS4 knockout complex I from Mus musculus hea... -
+
Open data
-
Basic information
Entry | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 3). | ||||||||||||
![]() | globally sharpened map | ||||||||||||
![]() |
| ||||||||||||
![]() | NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE | ||||||||||||
Function / homology | ![]() Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / blastocyst hatching / Mitochondrial protein degradation / cellular response to oxygen levels ...Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / blastocyst hatching / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / response to light intensity / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / negative regulation of insulin secretion involved in cellular response to glucose stimulus / cardiac muscle tissue development / negative regulation of non-canonical NF-kappaB signal transduction / : / [2Fe-2S] cluster assembly / oxygen sensor activity / cellular response to glucocorticoid stimulus / ubiquinone-6 biosynthetic process / positive regulation of mitochondrial membrane potential / respiratory chain complex I / response to hydroperoxide / cellular respiration / iron-sulfur cluster assembly / NADH dehydrogenase activity / mitochondrial ribosome / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / acyl binding / ubiquinone binding / acyl carrier activity / cellular response to interferon-beta / quinone binding / electron transport coupled proton transport / neurogenesis / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / ATP metabolic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / mitochondrial ATP synthesis coupled electron transport / mitochondrial respiratory chain complex I assembly / : / ionotropic glutamate receptor binding / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / cerebellum development / response to hormone / regulation of mitochondrial membrane potential / : / mitochondrial electron transport, NADH to ubiquinone / response to cocaine / synaptic membrane / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase (ubiquinone) activity / apoptotic signaling pathway / electron transport chain / response to nicotine / circadian rhythm / response to hydrogen peroxide / mitochondrial membrane / response to organic cyclic compound / aerobic respiration / mitochondrial intermembrane space / negative regulation of cell growth / 2 iron, 2 sulfur cluster binding / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding / protease binding / response to ethanol / in utero embryonic development / response to oxidative stress / response to hypoxia / nuclear body / electron transfer activity / mitochondrial inner membrane / nuclear speck / structural constituent of ribosome / mitochondrial matrix / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / neuronal cell body / ubiquitin protein ligase binding / synapse / dendrite / protein-containing complex binding / protein kinase binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
![]() | Yin Z / Bridges HR / Agip ANA / Hirst J | ||||||||||||
Funding support | ![]()
| ||||||||||||
![]() | ![]() Title: Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4 mouse. Authors: Zhan Yin / Ahmed-Noor A Agip / Hannah R Bridges / Judy Hirst / ![]() ![]() ![]() Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh ...Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4 mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4 mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4 mouse model and complex I-linked mitochondrial disease. | ||||||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 322.6 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 64.5 KB 64.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 15.9 KB | Display | ![]() |
Images | ![]() | 132 KB | ||
Masks | ![]() | 347.6 MB | ![]() | |
Filedesc metadata | ![]() | 14 KB | ||
Others | ![]() ![]() | 322.2 MB 322.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 23.4 KB | Display | |
Data in CIF | ![]() | 31.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ca5MC ![]() 8c2sC ![]() 8ca1C ![]() 8ca3C ![]() 8ca4C M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | globally sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.352 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map 1
File | emd_16518_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map 2
File | emd_16518_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
+Entire : Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
+Supramolecule #1: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
+Macromolecule #1: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2
+Macromolecule #2: NADH-ubiquinone oxidoreductase chain 3
+Macromolecule #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+Macromolecule #4: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+Macromolecule #5: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+Macromolecule #6: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+Macromolecule #7: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+Macromolecule #8: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
+Macromolecule #9: NADH-ubiquinone oxidoreductase chain 1
+Macromolecule #10: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+Macromolecule #11: NADH-ubiquinone oxidoreductase chain 6
+Macromolecule #12: NADH-ubiquinone oxidoreductase chain 4L
+Macromolecule #13: NADH-ubiquinone oxidoreductase chain 5
+Macromolecule #14: NADH-ubiquinone oxidoreductase chain 4
+Macromolecule #15: NADH-ubiquinone oxidoreductase chain 2
+Macromolecule #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mi...
+Macromolecule #17: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+Macromolecule #18: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+Macromolecule #19: Acyl carrier protein, mitochondrial
+Macromolecule #20: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+Macromolecule #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+Macromolecule #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+Macromolecule #23: MCG5603
+Macromolecule #24: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+Macromolecule #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+Macromolecule #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+Macromolecule #27: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+Macromolecule #28: NADH dehydrogenase [ubiquinone] 1 subunit C2
+Macromolecule #29: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+Macromolecule #30: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+Macromolecule #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+Macromolecule #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+Macromolecule #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+Macromolecule #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+Macromolecule #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+Macromolecule #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+Macromolecule #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+Macromolecule #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+Macromolecule #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+Macromolecule #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+Macromolecule #41: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+Macromolecule #42: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+Macromolecule #43: IRON/SULFUR CLUSTER
+Macromolecule #44: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #45: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+Macromolecule #46: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #47: FLAVIN MONONUCLEOTIDE
+Macromolecule #48: Ubiquinone-9
+Macromolecule #49: CARDIOLIPIN
+Macromolecule #50: DODECYL-BETA-D-MALTOSIDE
+Macromolecule #51: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #52: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #53: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 3.82 mg/mL | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7.14 Component:
Details: pH was corrected at room temperature ~22 C | |||||||||||||||
Grid | Model: UltrAuFoil / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.9 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |