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Structure paper

TitleThe coupling mechanism of mammalian mitochondrial complex I.
Journal, issue, pagesNat Struct Mol Biol, Vol. 29, Issue 2, Page 172-182, Year 2022
Publish dateFeb 10, 2022
AuthorsJinke Gu / Tianya Liu / Runyu Guo / Laixing Zhang / Maojun Yang /
PubMed AbstractMammalian respiratory complex I (CI) is a 45-subunit, redox-driven proton pump that generates an electrochemical gradient across the mitochondrial inner membrane to power ATP synthesis in ...Mammalian respiratory complex I (CI) is a 45-subunit, redox-driven proton pump that generates an electrochemical gradient across the mitochondrial inner membrane to power ATP synthesis in mitochondria. In the present study, we report cryo-electron microscopy structures of CI from Sus scrofa in six treatment conditions at a resolution of 2.4-3.5 Å, in which CI structures of each condition can be classified into two biochemical classes (active or deactive), with a notably higher proportion of active CI particles. These structures illuminate how hydrophobic ubiquinone-10 (Q10) with its long isoprenoid tail is bound and reduced in a narrow Q chamber comprising four different Q10-binding sites. Structural comparisons of active CI structures from our decylubiquinone-NADH and rotenone-NADH datasets reveal that Q10 reduction at site 1 is not coupled to proton pumping in the membrane arm, which might instead be coupled to Q10 oxidation at site 2. Our data overturn the widely accepted previous proposal about the coupling mechanism of CI.
External linksNat Struct Mol Biol / PubMed:35145322
MethodsEM (single particle)
Resolution2.4 - 3.5 Å
Structure data

EMDB-31640, PDB-7v2c:
Active state complex I from Q10 dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-31641, PDB-7v2d:
Deactive state complex I from Q10 dataset
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-31643, PDB-7v2e:
Active state complex I from Q10-NADH dataset
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-31644, PDB-7v2f:
Deactive state complex I from Q10-NADH dataset
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-31645, PDB-7v2h:
Active state complex I from DQ-NADH dataset
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-31646, PDB-7v2k:
Deactive state complex I from DQ-NADH dataset
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-31647, PDB-7v2r:
Active state complex I from Q1-NADH dataset
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-31648, PDB-7v30:
Deactive state complex I from Q1-NADH dataset
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-31649, PDB-7v31:
Active state complex I from rotenone dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-31650, PDB-7v32:
Deactive state complex I from rotenone dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-31651, PDB-7v33:
Active state complex I from rotenone-NADH dataset
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-31652, PDB-7v3m:
Deactive state complex I from rotenone-NADH dataset
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-31874, PDB-7vb7:
Matrix arm of active state CI from DQ-NADH dataset
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-31881, PDB-7vbl:
Membrane arm of active state CI from DQ-NADH dataset
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-31883, PDB-7vbn:
Matrix arm of deactive state CI from DQ-NADH dataset
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-31884, PDB-7vbp:
Membrane arm of deactive state CI from DQ-NADH dataset
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-31886, PDB-7vbz:
Matrix arm of active state CI from Rotenone-NADH dataset
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-31887, PDB-7vc0:
Membrane arm of active state CI from Rotenone-NADH dataset
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-32154, PDB-7vwj:
Matrix arm of deactive state CI from rotenone-NADH dataset
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-32155, PDB-7vwl:
Membrane arm of deactive state CI from rotenone-NADH dataset
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32186, PDB-7vxp:
Matrix arm of active state CI from Q10 dataset
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32187, PDB-7vxs:
Membrane arm of active state CI from Q10 dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32188, PDB-7vxu:
Matrix arm of deactive state CI from Q10 dataset
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-32191, PDB-7vy1:
Membrane arm of deactive state CI from Q10 dataset
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-32196, PDB-7vy8:
Matrix arm of active state CI from Q10-NADH dataset
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-32197, PDB-7vy9:
Membrane arm of active state CI from Q10-NADH dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32198, PDB-7vya:
Matrix arm of deactive state CI from Q10-NADH dataset
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-32202, PDB-7vye:
Membrane arm of deactive state CI from Q10-NADH dataset
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-32203, PDB-7vyf:
Matrix arm of active state CI from Rotenone dataset
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-32204, PDB-7vyg:
Membrane arm of active state CI from rotenone dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32205, PDB-7vyh:
Matrix arm of deactive state CI from Rotenone dataset
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32206, PDB-7vyi:
Membrane arm of deactive state CI from Rotenone dataset
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-32210, PDB-7vyn:
Matrix arm of active state CI from Q1-NADH dataset
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-32214, PDB-7vys:
Membrane arm of active state CI from Q1-NADH dataset
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-32218, PDB-7vz1:
Matrix arm of deactive state CI from Q1-NADH dataset
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-32222, PDB-7vz8:
Membrane arm of deactive state CI from Q1-NADH dataset
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32230, PDB-7vzv:
Active state CI from Q10 dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-32231, PDB-7vzw:
Active state CI from Q10 dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-32232, PDB-7w00:
Deactive state CI from Q10 dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-32242, PDB-7w0h:
Deactive state CI from Q10 dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-32248, PDB-7w0r:
Active state CI from Q10-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-32249, PDB-7w0y:
Active state CI from Q10-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-32253, PDB-7w1o:
Deactive state CI from Q10-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-32254, PDB-7w1p:
Deactive state CI from Q10-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-32255, PDB-7w1t:
Active state CI from Rotenone dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32256, PDB-7w1u:
Active state CI from Rotenone dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-32257, PDB-7w1v:
Active state CI from Rotenone-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32259, PDB-7w1z:
Active state CI from Rotenone-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-32260, PDB-7w20:
Active state CI from Rotenone-NADH dataset, Subclass 3
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32263, PDB-7w2k:
Deactive state CI from Rotenone-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32264, PDB-7w2l:
Deactive state CI from Rotenone-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32265, PDB-7w2r:
Active state CI from DQ-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32266, PDB-7w2u:
Active state CI from DQ-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-32267, PDB-7w2y:
Active state CI from DQ-NADH dataset, Subclass 3
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32269, PDB-7w31:
Deactive state CI from DQ-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-32270, PDB-7w32:
Deactive state CI from DQ-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-32271, PDB-7w35:
Deactive state CI from DQ-NADH dataset, Subclass 3
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32300, PDB-7w4c:
Active state CI from Q1-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32301, PDB-7w4d:
Active state CI from Q1-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32302, PDB-7w4e:
Active state CI from Q1-NADH dataset, Subclass 3
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32303, PDB-7w4f:
Active state CI from Q1-NADH dataset, Subclass 4
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-32304, PDB-7w4g:
Active state CI from Q1-NADH dataset, Subclass 5
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-32305, PDB-7w4j:
Deactive state CI from Q1-NADH dataset, Subclass 1
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-32306, PDB-7w4k:
Deactive state CI from Q1-NADH dataset, Subclass 2
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-32307, PDB-7w4l:
Deactive state CI from Q1-NADH dataset, Subclass 3
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-32308, PDB-7w4m:
Deactive state CI from Q1-NADH dataset, Subclass 4
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-32309, PDB-7w4n:
Deactive state CI from Q1-NADH dataset, Subclass 5
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-32312, PDB-7w4q:
Deactive state CI from Q1-NADH dataset, Subclass 6
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM / Discrete optimized protein energy

ChemComp-PLX:
(9R,11S)-9-({[(1S)-1-HYDROXYHEXADECYL]OXY}METHYL)-2,2-DIMETHYL-5,7,10-TRIOXA-2LAMBDA~5~-AZA-6LAMBDA~5~-PHOSPHAOCTACOSANE-6,6,11-TRIOL / phospholipid*YM

ChemComp-8Q1:
S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate

ChemComp-NDP:
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate

ChemComp-UQ:
Coenzyme Q10, (2Z,6E,10Z,14E,18E,22E,26Z)-isomer

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-NAI:
1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / Nicotinamide adenine dinucleotide

ChemComp-DCQ:
2-decyl-5,6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione

ChemComp-UQ1:
UBIQUINONE-1

ChemComp-970:
(2R,6aS,12aS)-8,9-dimethoxy-2-(prop-1-en-2-yl)-1,2,12,12a-tetrahydrofuro[2',3':7,8][1]benzopyrano[2,3-c][1]benzopyran-6(6aH)-one / Rotenone

ChemComp-HOH:
WATER / Water

ChemComp-TYR:
TYROSINE / Tyrosine

Source
  • sus scrofa (pig)
  • pig (pig)
KeywordsELECTRON TRANSPORT / Respiratory / Complex / mammalian / complex I / mitochondrial / ELECTRON T

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