An ancestral interaction module promotes oligomerization in divergent mitochondrial ATP synthases

Abstract

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 trypanosomes in 10 different rotational states. The model consists of 25 subunits, including 11 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 and -e form a common ancestral oligomerisation 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.

Characterization of a highly diverged mitochondrial ATP synthase Fo subunit in Trypanosoma brucei

“…While the present study was under revision, the structure of the F 1 F o ATP synthase dimer of T. brucei was reported ( 73 ), which surprisingly appears to contain a subunit b homolog that is different from Tb927.8.3070. This seems to favor the interpretation that Tb927.8.3070 is a late assembly factor rather than being subunit b ; however, it cannot be excluded that trypanosomal F 1 F o ATP synthase complexes might be heterogenous and contain different subunit b -like proteins.…”

Algal photosystem I dimer and high-resolution model of PSI-plastocyanin complex

“…This allows eukaryotic cells to adapt metabolically to nutrient and proteome limitations. Crowding of large complexes in the membrane systems of thylakoid 35,36 and mitochondrial cristae 37 , as well as in the cytosol, for example, ribosome dimers 38 , is an established and conserved mechanism for a more efficient differentiation of functions, ecological adaptation and material storage during less active periods. As the basic structure of the PSI core is rigid and it operates according to conserved mechanisms, the regulation by PsaH/Lhca2 provides a degree of flexibility on the macromolecular level that would allow the photosynthetic apparatus to adapt to stresses and tolerate changes in the range of light intensities that might involve membrane re-organization 15,39 .…”

Algal photosystem I dimer and high resolution model of PSI:plastocyanin complex

“…This allows eukaryotic cells to adapt metabolically to nutrient and proteome limitations. Crowding of large complexes in the membrane systems of thylakoid 35, 36 , mitochondrial cristae 37 , as well as in the cytosol, e.g. ribosome dimers 38 is an established and conserved mechanism for a more efficient differentiation of functions, ecological adaptation, and material storage during less active periods.…”