ATPB

ATPB is the beta subunit of the divergent mitochondrial F-type (F1Fo) ATP synthase of Toxoplasma gondii, a complex whose organization shapes the parasite's characteristic tubular cristae (PMID:30005062, PMID:33402698). The complex was purified as monomeric (~600 kDa) and dimeric (>1 MDa) native forms, and mass spectrometry, complexome profiling, and cryo-EM together established a highly divergent subunit composition, with core subunits accompanied by roughly 17 apicomplexan-specific accessory subunits, extensively diversified FO subunits a, b, and d, and bound cardiolipins and the inhibitor IF1 at the dimer interface (PMID:30005062, PMID:33402698, PMID:33651838). Cryo-EM and cryo-ET showed that the ATP synthase assembles into cyclic hexamers that further arrange into ~20-MDa pentagonal pyramidal arrays at curved apical inner-membrane regions, an architecture required for normal cristae morphology, as knockout of the linker subunit ATPTG11 disrupted the pyramids and produced aberrant cristae (PMID:33402698). Beyond its identity as a subunit of this structurally characterized complex, no ATPB-specific mechanistic detail has been characterized in the available corpus.

1. 2018 Medium

   It was unknown how the apicomplexan ATP synthase, including its beta subunit ATPB, was organized; native purification established that the complex exists in defined monomeric and dimeric states and carries an unexpectedly large complement of novel subunits.

   Evidence Partial purification of the native complex followed by mass spectrometry and bioinformatic identification of conserved FO features in T. gondii

   PMID:30005062

   Open questions at the time

   • No high-resolution structure of the complex or placement of ATPB within it
   • No direct functional assay of ATP synthase activity
   • Role of individual subunits, including ATPB, not tested genetically
2. 2021 High

   The three-dimensional architecture and physiological role of the complex were resolved, showing that the ATP synthase forms cyclic hexamers assembling into pentagonal pyramids that dictate cristae shape.

   Evidence Cryo-EM structure of the hexamer, cryo-ET with subtomogram averaging, and genetic knockout of linker subunit ATPTG11 with cristae phenotyping in T. gondii

   PMID:33402698

   Open questions at the time

   • Specific catalytic or structural contribution of ATPB within the hexamer not individually dissected
   • Consequence of ATPB loss for parasite viability not tested
3. 2021 Medium

   A systematic inventory of the complex confirmed and extended the divergent subunit composition, assigning proteins to the F1Fo-ATP synthase and identifying additional uncharacterized subunits.

   Evidence Complexome profiling by blue-native PAGE coupled with quantitative mass spectrometry of T. gondii mitochondria

   PMID:33651838

   Open questions at the time

   • Assignment is compositional, not functional, for ATPB
   • Stoichiometry and assembly order of ATPB not resolved