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TitleCryo-EM structure of the entire mammalian F-type ATP synthase.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 11, Page 1077-1085, Year 2020
Publish dateSep 14, 2020
AuthorsGergely Pinke / Long Zhou / Leonid A Sazanov /
PubMed AbstractThe majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain ...The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the 'proton translocation cluster' attached to the c-ring and a more distant 'hook apparatus' holding subunit e. Unexpectedly, this subunit is anchored to a lipid 'plug' capping the c-ring. We present a detailed proton translocation pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled c-ring, suggesting permeability transition pore opening. We propose a model for the permeability transition pore opening, whereby subunit e pulls the lipid plug out of the c-ring. Our structure will allow the design of drugs for many emerging applications in medicine.
External linksNat Struct Mol Biol / PubMed:32929284
MethodsEM (single particle)
Resolution3.5 - 3.76 Å
Structure data

10573

6tt7

EMDB-10573, PDB-6tt7:
Ovine ATP synthase 1a state
Method: EM (single particle) / Resolution: 3.5 Å

11127

6za9

EMDB-11127, PDB-6za9:
Fo domain of Ovine ATP synthase
Method: EM (single particle) / Resolution: 3.76 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-LHG:
1,2-DIPALMITOYL-PHOSPHATIDYL-GLYCEROLE / phospholipid*YM

ChemComp-P5S:
O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-S12:
O-[(S)-hydroxy{[(2S)-2-hydroxy-3-(octadec-9-enoyloxy)propyl]oxy}phosphoryl]-L-serine

Source
  • ovis aries (sheep)
KeywordsMEMBRANE PROTEIN / ATP synthase / mitochondrial / respiratory chain / mammalian

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