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TitleMitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 10, Page 892-900, Year 2020
Publish dateAug 3, 2020
AuthorsDaniel N Grba / Judy Hirst /
PubMed AbstractMitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. ...Mitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. Recent cryo-EM analyses of mammalian and yeast complex I have revolutionized structural and mechanistic knowledge and defined structures in different functional states. Here, we describe a 2.7-Å-resolution structure of the 42-subunit complex I from the yeast Yarrowia lipolytica containing 275 structured water molecules. We identify a proton-relay pathway for ubiquinone reduction and water molecules that connect mechanistically crucial elements and constitute proton-translocation pathways through the membrane. By comparison with known structures, we deconvolute structural changes governing the mammalian 'deactive transition' (relevant to ischemia-reperfusion injury) and their effects on the ubiquinone-binding site and a connected cavity in ND1. Our structure thus provides important insights into catalysis by this enigmatic respiratory machine.
External linksNat Struct Mol Biol / PubMed:32747785 / PubMed Central
MethodsEM (single particle)
Resolution2.7 Å
Structure data

10815

6yj4

EMDB-10815, PDB-6yj4:
Structure of Yarrowia lipolytica complex I at 2.7 A
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

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

ChemComp-SF4:
IRON/SULFUR CLUSTER

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

ChemComp-PLC:
DIUNDECYL PHOSPHATIDYL CHOLINE / phospholipid*YM

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

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

ChemComp-HOH:
WATER

Source
  • yarrowia lipolytica (yeast)
  • yarrowia lipolytica (strain clib 122 / e 150) (yeast)
KeywordsMEMBRANE PROTEIN / NADH:Ubiquinone Oxidoreductase / complex I

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