An ancestral interaction module promotes oligomerization in divergent mitochondrial ATP synthases.

Gahura O, Mühleip A, Hierro-Yap C, Panicucci B, Jain M, Hollaus D, Slapničková M, Zíková A, Amunts A

Nat Commun 13 (1) 5989 [2022-10-11; online 2022-10-11]

Mitochondrial ATP synthase forms stable dimers arranged into oligomeric assemblies that generate the inner-membrane curvature essential for efficient energy conversion. Here, we report cryo-EM structures of the intact ATP synthase dimer from Trypanosoma brucei in ten different rotational states. The model consists of 25 subunits, including nine lineage-specific, as well as 36 lipids. The rotary mechanism is influenced by the divergent peripheral stalk, conferring a greater conformational flexibility. Proton transfer in the lumenal half-channel occurs via a chain of five ordered water molecules. The dimerization interface is formed by subunit-g that is critical for interactions but not for the catalytic activity. Although overall dimer architecture varies among eukaryotes, we find that subunit-g together with subunit-e form an ancestral oligomerization motif, which is shared between the trypanosomal and mammalian lineages. Therefore, our data defines the subunit-g/e module as a structural component determining ATP synthase oligomeric assemblies.

PubMed 36220811

DOI 10.1038/s41467-022-33588-z

Crossref 10.1038/s41467-022-33588-z

pmc: PMC9553925
pii: 10.1038/s41467-022-33588-z