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TitleATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 120, Year 2021
Publish dateJan 5, 2021
AuthorsAlexander Mühleip / Rasmus Kock Flygaard / Jana Ovciarikova / Alice Lacombe / Paula Fernandes / Lilach Sheiner / Alexey Amunts /
PubMed AbstractMitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has ...Mitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has been observed, but its structural basis is unknown. Here, we report that the apicomplexan ATP synthase assembles into cyclic hexamers, essential to shape their distinct cristae. Cryo-EM was used to determine the structure of the hexamer, which is held together by interactions between parasite-specific subunits in the lumenal region. Overall, we identified 17 apicomplexan-specific subunits, and a minimal and nuclear-encoded subunit-a. The hexamer consists of three dimers with an extensive dimer interface that includes bound cardiolipins and the inhibitor IF. Cryo-ET and subtomogram averaging revealed that hexamers arrange into ~20-megadalton pentagonal pyramids in the curved apical membrane regions. Knockout of the linker protein ATPTG11 resulted in the loss of pentagonal pyramids with concomitant aberrantly shaped cristae. Together, this demonstrates that the unique macromolecular arrangement is critical for the maintenance of cristae morphology in Apicomplexa.
External linksNat Commun / PubMed:33402698 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging)
Resolution2.8 - 34.0 Å
Structure data

EMDB-10520: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, membrane region map
PDB-6tmg: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, membrane region model
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-10521: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, OSCP/F1/c-ring map
PDB-6tmh: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, OSCP/F1/c-ring model
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-10522: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, peripheral stalk map
PDB-6tmi: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, peripheral stalk model
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-10523: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, rotor-stator map
PDB-6tmj: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, rotor-stator model
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-10524: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, consensus map
PDB-6tmk: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, composite model
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-10525: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase hexamer, membrane region
PDB-6tml: Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase hexamer, composite model
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-10526:
Subtomogram average of ATP synthase dimer from Toxoplasma gondii mitochondrial membranes
Method: EM (subtomogram averaging) / Resolution: 20.0 Å

EMDB-10527:
Subtomogram average of the ATP synthase dimer from Toxoplasma gondii mitochondria
Method: EM (subtomogram averaging) / Resolution: 34.0 Å

EMDB-11403:
Subtomogram average of the ATP synthase dimer from Toxoplasma gondii ATPTG11-KO mitochondrial membranes
Method: EM (subtomogram averaging) / Resolution: 22.0 Å

Chemicals

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

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

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

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

Source
  • toxoplasma gondii gt1 (eukaryote)
  • toxoplasma gondii (strain atcc 50853 / gt1) (eukaryote)
KeywordsMEMBRANE PROTEIN / mitochondrial / ATP synthase / membrane region / lipids / F1 / c-ring / peripheral stalk / OSCP / rotor / stator / dimer / hexamer

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