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Structure paper

TitleResting mitochondrial complex I from adopts a helix-locked state.
Journal, issue, pagesElife, Vol. 12, Year 2023
Publish dateMar 23, 2023
AuthorsAbhilash Padavannil / Anjaneyulu Murari / Shauna-Kay Rhooms / Edward Owusu-Ansah / James A Letts /
PubMed AbstractRespiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the ...Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt a biochemically defined off-pathway 'deactive' state, whereas complex I from Protostomia cannot. The presence of off-pathway states complicates the interpretation of structural results and has led to considerable mechanistic debate. Here, we report the structure of mitochondrial complex I from the thoracic muscles of the model protostome . We show that although complex I (-CI) does not have a NEM-sensitive deactive state, it does show slow activation kinetics indicative of an off-pathway resting state. The resting-state structure of -CI from the thoracic muscle reveals multiple conformations. We identify a helix-locked state in which an N-terminal α-helix on the NDUFS4 subunit wedges between the peripheral and membrane arms. Comparison of the -CI structure and conformational states to those observed in bacteria, yeast, and mammals provides insight into the roles of subunits across organisms, explains why the -CI off-pathway resting state is NEM insensitive, and raises questions regarding current mechanistic models of complex I turnover.
External linksElife / PubMed:36952377 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.4 Å
Structure data

EMDB-28581, PDB-8esw:
Structure of mitochondrial complex I from Drosophila melanogaster, Flexible-class 1
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-28582, PDB-8esz:
Structure of mitochondrial complex I from Drosophila melanogaster, Helix-locked state
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

ChemComp-ZN:
Unknown entry

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

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

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM / Phosphatidylethanolamine

ChemComp-ZMP:
S-[2-({N-[(2S)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] tetradecanethioate

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

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

ChemComp-DGT:
2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE / Deoxyguanosine triphosphate

ChemComp-U10:
UBIQUINONE-10 / Coenzyme Q10

ChemComp-C14:
TETRADECANE / Tetradecane

ChemComp-OCT:
N-OCTANE / Octane

ChemComp-D12:
DODECANE / Dodecane

ChemComp-WSF:
(2R)-3-{[(S)-hydroxy(3-methylbutoxy)phosphoryl]oxy}-2-(octanoyloxy)propyl decanoate

Source
  • drosophila melanogaster (fruit fly)
  • fruit fly (fruit fly)
KeywordsOXIDOREDUCTASE / NADH:ubiquinone oxidoreductase / TRANSLOCASE

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