ICAP2

ICAP2 is a Toxoplasma gondii-specific subunit of the mitochondrial ATP synthase complex, where it acts as a structural component required for complex integrity and mitochondrial function (PMID:30204085). Structural modeling places it as distantly related to mammalian stator subunits, and co-immunoprecipitation confirms its physical incorporation into the ATP synthase complex (PMID:30204085). Conditional depletion of ICAP2 disassembles the ATP synthase complex and produces aberrant mitochondrial morphology and decreased oxygen consumption, establishing that it is essential for maintaining ATP synthase assembly and oxidative respiration (PMID:30204085). Beyond this single characterization (PMID:30204085), no further mechanistic detail has been established in the available corpus.

1. 2018 High

   It was unknown which subunits maintain the structural integrity of the divergent Toxoplasma ATP synthase; identifying ICAP2 as a stator-like subunit established a specific structural determinant of complex assembly and mitochondrial respiration.

   Evidence Protein complex identification, structural modeling, co-immunoprecipitation, and conditional depletion with mitochondrial morphology, oxygen consumption, and complex-assembly readouts in Toxoplasma gondii

   PMID:30204085

   Open questions at the time

   • The precise molecular interactions ICAP2 makes within the ATP synthase (which subunits it contacts) are not resolved
   • No structural model beyond distant homology to mammalian stator subunits
   • Whether ICAP2 has roles outside ATP synthase assembly is not addressed

• The atomic-level architecture of ICAP2 within the ATP synthase and its direct binding partners remain undefined.
• No high-resolution structure of the ICAP2-containing ATP synthase
• Direct binding partners within the complex not mapped
• Functional conservation across apicomplexan species not tested