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- PDB-8uca: Formation of I2+III2 supercomplex rescues respiratory chain defects -
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Basic information
Entry | Database: PDB / ID: 8uca | ||||||
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Title | Formation of I2+III2 supercomplex rescues respiratory chain defects | ||||||
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![]() | ELECTRON TRANSPORT / Translocase / Super complex XL (CI2+CIII2) | ||||||
Function / homology | ![]() Complex III assembly / subthalamus development / pons development / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / cerebellar Purkinje cell layer development ...Complex III assembly / subthalamus development / pons development / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / cerebellar Purkinje cell layer development / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / response to mercury ion / protein insertion into mitochondrial inner membrane / mesenchymal stem cell differentiation / circulatory system development / pyramidal neuron development / blastocyst hatching / thalamus development / mitochondrial respiratory chain complex III assembly / respiratory system process / psychomotor behavior / cellular respiration / Mitochondrial protein degradation / cellular response to oxygen levels / respiratory chain complex / stem cell division / response to light intensity / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / response to copper ion / gliogenesis / response to alkaloid / respiratory chain complex III / negative regulation of non-canonical NF-kappaB signal transduction / response to glucagon / cardiac muscle tissue development / neural precursor cell proliferation / [2Fe-2S] cluster assembly / quinol-cytochrome-c reductase / positive regulation of mitochondrial membrane potential / adult walking behavior / cellular response to glucocorticoid stimulus / oxygen sensor activity / quinol-cytochrome-c reductase activity / response to hydroperoxide / mitochondrial electron transport, ubiquinol to cytochrome c / hypothalamus development / iron-sulfur cluster assembly / positive regulation of ATP biosynthetic process / midbrain development / response to cobalamin / electron transport coupled proton transport / dopamine metabolic process / adult behavior / NADH:ubiquinone reductase (H+-translocating) / mitochondrial respiratory chain complex I assembly / positive regulation of execution phase of apoptosis / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase activity / respiratory chain complex I / response to hyperoxia / NADH dehydrogenase (ubiquinone) activity / animal organ regeneration / neuron development / quinone binding / cellular response to interferon-beta / response to cadmium ion / ATP synthesis coupled electron transport / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / tricarboxylic acid cycle / muscle contraction / response to hormone / DNA damage response, signal transduction by p53 class mediator / Neutrophil degranulation / visual perception / cerebellum development / reactive oxygen species metabolic process / aerobic respiration / regulation of mitochondrial membrane potential / hippocampus development / kidney development / respiratory electron transport chain / response to activity / neurogenesis / fatty acid metabolic process / mitochondrion organization / response to nicotine / sensory perception of sound / response to cocaine / monooxygenase activity / electron transport chain / mitochondrial membrane / : / brain development Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
![]() | Letts, J.A. / Padavannil, A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Formation of I+III supercomplex rescues respiratory chain defects. Authors: Chao Liang / Abhilash Padavannil / Shan Zhang / Sheryl Beh / David R L Robinson / Jana Meisterknecht / Alfredo Cabrera-Orefice / Timothy R Koves / Chika Watanabe / Miyuki Watanabe / María ...Authors: Chao Liang / Abhilash Padavannil / Shan Zhang / Sheryl Beh / David R L Robinson / Jana Meisterknecht / Alfredo Cabrera-Orefice / Timothy R Koves / Chika Watanabe / Miyuki Watanabe / María Illescas / Radiance Lim / Jordan M Johnson / Shuxun Ren / Ya-Jun Wu / Dennis Kappei / Anna Maria Ghelli / Katsuhiko Funai / Hitoshi Osaka / Deborah Muoio / Cristina Ugalde / Ilka Wittig / David A Stroud / James A Letts / Lena Ho / ![]() ![]() ![]() ![]() ![]() ![]() ![]() Abstract: Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the ...Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.7 Å by cryoelectron microscopy (cryo-EM). SC-XL formation increases mitochondrial cristae density, reduces CIII reactive oxygen species (ROS), and sustains normal respiration despite a 70% reduction in CIII activity, effectively rescuing CIII deficiency. Consequently, inhibiting SC-XL formation in CIII mutants using the Uqcrc1 contact site mutation leads to respiratory decompensation. Lastly, SC-XL formation promotes fatty acid oxidation (FAO) and protects against ischemic heart failure in mice. Our study uncovers an unexpected plasticity in the mammalian ETC, where structural adaptations mitigate intrinsic perturbations, and suggests that manipulating SC-XL formation is a potential therapeutic strategy for mitochondrial dysfunction. | ||||||
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-Validation report
Summary document | ![]() | 2.8 MB | Display | ![]() |
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Full document | ![]() | 2.9 MB | Display | |
Data in XML | ![]() | 440.2 KB | Display | |
Data in CIF | ![]() | 705.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 42122MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
Experimental dataset #1 | Data reference: ![]() |
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Assembly
Deposited unit | ![]()
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Components
-NADH-ubiquinone oxidoreductase chain ... , 7 types, 14 molecules 33a11a66a4L4l55a44a22a
#1: Protein | Mass: 13223.775 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #4: Protein | Mass: 36105.027 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q4JFN6, NADH:ubiquinone reductase (H+-translocating) #5: Protein | Mass: 18628.090 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P03925, NADH:ubiquinone reductase (H+-translocating) #6: Protein | Mass: 10609.619 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P03903, NADH:ubiquinone reductase (H+-translocating) #7: Protein | Mass: 68519.289 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P03921, NADH:ubiquinone reductase (H+-translocating) #8: Protein | Mass: 51915.535 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P03911, NADH:ubiquinone reductase (H+-translocating) #9: Protein | Mass: 38772.219 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P03893, NADH:ubiquinone reductase (H+-translocating) |
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-NADH dehydrogenase [ubiquinone] iron-sulfur protein ... , 7 types, 14 molecules S3s3S2s2S4s4S6s6S5s5S7s7S8s8
#2: Protein | Mass: 30191.307 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q9DCT2, NADH:ubiquinone reductase (H+-translocating) #3: Protein | Mass: 52720.602 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q91WD5, NADH:ubiquinone reductase (H+-translocating) #12: Protein | Mass: 19814.725 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #13: Protein | Mass: 13041.828 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #25: Protein | Mass: 12675.772 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #54: Protein | Mass: 24715.912 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q9DC70, NADH:ubiquinone reductase (H+-translocating) #55: Protein | Mass: 24068.355 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q8K3J1, NADH:ubiquinone reductase (H+-translocating) |
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-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 12 types, 24 molecules ALalA9a9A2a2A5a5A6a6A8a8AMamAOaoA1a1A3a3ANanA7a7
#10: Protein | Mass: 40657.375 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #11: Protein | Mass: 42588.129 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #14: Protein | Mass: 10932.675 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #16: Protein | Mass: 13380.719 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #17: Protein | Mass: 15311.858 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #18: Protein | Mass: 20025.127 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #19: Protein | Mass: 14999.220 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #20: Protein | Mass: 16881.588 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #21: Protein | Mass: 8149.524 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #22: Protein | Mass: 9338.867 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #37: Protein | Mass: 17112.416 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #38: Protein | Mass: 12464.396 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Protein , 4 types, 10 molecules ABACabac3C3N3D3OS1s1
#15: Protein | Mass: 17390.289 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #42: Protein | Mass: 43143.191 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #43: Protein | Mass: 27312.188 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #53: Protein | Mass: 78781.484 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q91VD9, NADH:ubiquinone reductase (H+-translocating) |
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-NADH dehydrogenase [ubiquinone] 1 subunit ... , 2 types, 4 molecules C1c1C2c2
#23: Protein | Mass: 8636.023 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #24: Protein | Mass: 14185.692 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit ... , 11 types, 22 molecules B1b1BMbmB5b5B6b6B2b2B3b3B8b8B4b4B9b9B7b7BLbl
#26: Protein | Mass: 6965.109 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #27: Protein | Mass: 17463.727 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #28: Protein | Mass: 21742.197 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #29: Protein | Mass: 15408.890 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #30: Protein | Mass: 11982.437 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #31: Protein | Mass: 11714.240 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #32: Protein | Mass: 21903.828 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #33: Protein | Mass: 15105.287 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #34: Protein | Mass: 22020.123 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #35: Protein | Mass: 16229.606 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #36: Protein | Mass: 21054.832 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-NADH dehydrogenase [ubiquinone] flavoprotein ... , 3 types, 6 molecules V3v3V1v1V2v2
#39: Protein | Mass: 11833.504 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #51: Protein | Mass: 50132.305 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q91YT0, NADH:ubiquinone reductase (H+-translocating) #52: Protein | Mass: 26948.918 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: Q9D6J6, NADH:ubiquinone reductase (H+-translocating) |
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-Cytochrome b-c1 complex subunit ... , 9 types, 17 molecules 3A3L3B3M3E3P3F3Q3G3R3H3S3J3U3K3V3T
#40: Protein | Mass: 49355.301 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #41: Protein | Mass: 46641.773 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #44: Protein | Mass: 21524.398 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #45: Protein | Mass: 13456.336 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #46: Protein | Mass: 9652.051 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #47: Protein | Mass: 9002.015 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #48: Protein | Mass: 7326.330 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #49: Protein | Mass: 6546.627 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #50: Protein | | Mass: 7900.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Non-polymers , 10 types, 36 molecules 


















#56: Chemical | #57: Chemical | #58: Chemical | #59: Chemical | #60: Chemical | ChemComp-EHZ / ~{ #61: Chemical | ChemComp-HEM / #62: Chemical | #63: Chemical | #64: Chemical | ChemComp-SF4 / #65: Chemical | ChemComp-FES / |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Mitochondrial Super-complex with CI dimer and CIII dimer (Super-complex XL) Type: COMPLEX / Entity ID: #1-#9, #12, #14, #16-#41, #45-#50 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 182132 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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