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TitleCryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.
Journal, issue, pagesNat Struct Mol Biol, Vol. 25, Issue 7, Page 548-556, Year 2018
Publish dateJun 18, 2018
AuthorsAhmed-Noor A Agip / James N Blaza / Hannah R Bridges / Carlo Viscomi / Shaun Rawson / Stephen P Muench / Judy Hirst /
PubMed AbstractComplex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian ...Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the 'active' state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the 'deactive' state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I.
External linksNat Struct Mol Biol / PubMed:29915388 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.9 Å
Structure data

4345

6g2j

EMDB-4345, PDB-6g2j:
Mouse mitochondrial complex I in the active state
Method: EM (single particle) / Resolution: 3.3 Å

4356

6g72

EMDB-4356, PDB-6g72:
Mouse mitochondrial complex I in the deactive state
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

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

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE

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

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*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-ACE:
ACETYL GROUP

Source
  • mus musculus (house mouse)
  • Mouse (mice)
KeywordsOXIDOREDUCTASE / Complex I / mitochondria / proton pump / membrane protein

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