6TMH

Cryo-EM structure of Toxoplasma gondii mitochondrial ATP synthase dimer, OSCP/F1/c-ring model

Summary for 6TMH

• Entry DOI: 10.2210/pdb6tmh/pdb
• EMDB information: 10521
• Descriptor: Inhibitor of F1, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (11 entities in total)
• Functional Keywords: mitochondrial, atp synthase, f1, c-ring, membrane protein
• Biological source: Toxoplasma gondii (strain ATCC 50853 / GT1); More
• Total number of polymer chains: 21
• Total formula weight: 649929.24

Authors

Muhleip, A.,Kock Flygaard, R.,Amunts, A. (deposition date: 2019-12-04, release date: 2020-12-16, Last modification date: 2024-05-22)

Primary citation

Muhleip, A.,Kock Flygaard, R.,Ovciarikova, J.,Lacombe, A.,Fernandes, P.,Sheiner, L.,Amunts, A.
ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria.
Nat Commun, 12:120-120, 2021

PubMed Abstract: 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.

PubMed: 33402698
DOI: 10.1038/s41467-020-20381-z

Experimental method

ELECTRON MICROSCOPY (3.1 Å)