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Structure paper

TitleCryo-EM structures of mitochondrial respiratory complex I from .
Journal, issue, pagesElife, Vol. 12, Year 2023
Publish dateJan 9, 2023
AuthorsAhmed-Noor A Agip / Injae Chung / Alvaro Sanchez-Martinez / Alexander J Whitworth / Judy Hirst /
PubMed AbstractRespiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. is a ...Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the enzyme is the mammalian-type 'ready-to-go' active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type 'deactive' pronounced resting state is not observed: in two minor states, the ubiquinone-binding site is unchanged, but a deactive-type π-bulge is present in ND6-TMH3. Our detailed structural knowledge of complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology.
External linksElife / PubMed:36622099 / PubMed Central
MethodsEM (single particle)
Resolution3.28 - 3.96 Å
Structure data

15936

8b9z

EMDB-15936, PDB-8b9z:
Drosophila melanogaster complex I in the Active state (Dm1)
Method: EM (single particle) / Resolution: 3.28 Å

15937

8ba0

EMDB-15937, PDB-8ba0:
Drosophila melanogaster complex I in the Twisted state (Dm2)
Method: EM (single particle) / Resolution: 3.68 Å

EMDB-15938: Drosophila melanogaster complex I in the Cracked state (Dm3)
Method: EM (single particle) / Resolution: 3.96 Å

Chemicals

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

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

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE

ChemComp-NA:
Unknown entry

ChemComp-UQ9:
Ubiquinone-9

ChemComp-DGT:
2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE

ChemComp-NDP:
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

ChemComp-ZN:
Unknown entry

ChemComp-EHZ:
~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butanoyl]amino]propanoylamino]ethyl] (3~{S})-3-oxidanyltetradecanethioate

Source
  • drosophila melanogaster (fruit fly)
  • fruit fly (fruit fly)
KeywordsOXIDOREDUCTASE / Mitochondrial complex I / Respiratory complex I / NADH:ubiquinone oxidoreductase / Ubiquinone

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