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Structure paper

TitleConformational changes in mitochondrial complex I of the thermophilic eukaryote .
Journal, issue, pagesSci Adv, Vol. 8, Issue 47, Page eadc9952, Year 2022
Publish dateNov 25, 2022
AuthorsEike Laube / Jakob Meier-Credo / Julian D Langer / Werner Kühlbrandt /
PubMed AbstractMitochondrial complex I is a redox-driven proton pump that generates proton-motive force across the inner mitochondrial membrane, powering oxidative phosphorylation and ATP synthesis in eukaryotes. ...Mitochondrial complex I is a redox-driven proton pump that generates proton-motive force across the inner mitochondrial membrane, powering oxidative phosphorylation and ATP synthesis in eukaryotes. We report the structure of complex I from the thermophilic fungus , determined by cryoEM up to 2.4-Å resolution. We show that the complex undergoes a transition between two conformations, which we refer to as state 1 and state 2. The conformational switch is manifest in a twisting movement of the peripheral arm relative to the membrane arm, but most notably in substantial rearrangements of the Q-binding cavity and the E-channel, resulting in a continuous aqueous passage from the E-channel to subunit ND5 at the far end of the membrane arm. The conformational changes in the complex interior resemble those reported for mammalian complex I, suggesting a highly conserved, universal mechanism of coupling electron transport to proton pumping.
External linksSci Adv / PubMed:36427319 / PubMed Central
MethodsEM (single particle)
Resolution2.44 - 2.83 Å
Structure data

EMDB-14791, PDB-7zm7:
CryoEM structure of mitochondrial complex I from Chaetomium thermophilum (inhibited by DDM)
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-14792, PDB-7zm8:
CryoEM structure of mitochondrial complex I from Chaetomium thermophilum (inhibited by DDM) - membrane arm
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-14794, PDB-7zmb:
CryoEM structure of mitochondrial complex I from Chaetomium thermophilum (state 2)
Method: EM (single particle) / Resolution: 2.75 Å

EMDB-14796, PDB-7zme:
CryoEM structure of mitochondrial complex I from Chaetomium thermophilum (state 2) - membrane arm
Method: EM (single particle) / Resolution: 2.83 Å

EMDB-14797, PDB-7zmg:
CryoEM structure of mitochondrial complex I from Chaetomium thermophilum (state 1)
Method: EM (single particle) / Resolution: 2.44 Å

EMDB-14798, PDB-7zmh:
CryoEM structure of mitochondrial complex I from Chaetomium thermophilum (state 1) - membrane arm
Method: EM (single particle) / Resolution: 2.47 Å

Chemicals

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

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

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

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

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

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

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

ChemComp-ZN:
Unknown entry

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

ChemComp-HOH:
WATER / Water

ChemComp-LMN:
Lauryl Maltose Neopentyl Glycol / detergent*YM

Source
  • chaetomium thermophilum var. thermophilum dsm 1495 (fungus)
KeywordsOXIDOREDUCTASE / Proton transporter / Mitochondrial membrane protein / Complex

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