In situ structure of trypanosomal ATP synthase dimer reveals a unique arrangement of catalytic subunits

Significance The mitochondrial F 1 F o ATP synthase is an essential membrane protein machine that supplies all eukaryotic cells with ATP. The proton-driven rotation of the rotor assembly in the membrane transmits energy to the catalytic F 1 head, where ATP is generated by rotary catalysis. We determined the in situ structures of ATP synthase dimers from the lethal human parasite Trypanosoma brucei and its free-living relative Euglena gracilis. In both ATP synthases, the catalytic subunits form a threefold pyramid rather than the usual near-sixfold ring. This unexpected finding indicates that the structure of the F 1 head, and therefore its catalytic action, is less highly conserved than previously thought, and provides insight into the fundamental mechanism of ATP production in higher organisms.