QCR7

QCR7 (PF3D7_1012300) is a subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), identified through its co-migration at ~730 kDa with the CIII dimer components CYTB, CYTC1, the Rieske subunit, QCR8, QCR9, MPPα/β, and Apicomplexa-specific subunits by complexome profiling (PMID:34155201). Its physical association within this complex is corroborated by chemoproteomic enrichment with a photoactivatable derivative of the antimalarial 9-methoxystrobilurin G (PMID:39262389) and by atovaquone-induced stabilisation in solvent proteome profiling (PMID:41308470), both consistent with membership in the drug-targeted Complex III. Beyond establishing QCR7 as a constituent of Complex III, the available corpus defines no catalytic activity, direct drug-binding role, or independent function for QCR7 itself.

1. 2021 High

   Establishing which proteins constitute the P. falciparum Complex III was needed to define the parasite's respiratory chain organization; complexome profiling placed QCR7 within the CIII dimer.

   Evidence Blue-native PAGE fractionation coupled to quantitative mass spectrometry across asexual blood stages and gametocytes, showing co-migration at ~730 kDa

   PMID:34155201

   Open questions at the time

   • Co-migration establishes complex membership but not a specific structural or catalytic role for QCR7
   • No stoichiometry or direct interaction partner within the complex is resolved for QCR7
   • No structural model of QCR7 in the assembled complex
2. 2024 Medium

   Whether QCR7 is physically accessible to Complex III-targeting antimalarials was unknown; chemoproteomic profiling showed a 9MG-derived probe enriches QCR7.

   Evidence Chemoproteomic target profiling using a photoactivatable derivative of 9-methoxystrobilurin G (photo-crosslinking enrichment) in P. falciparum 3D7

   PMID:39262389

   Open questions at the time

   • Single lab, single chemoproteomic method; enrichment does not distinguish direct probe binding to QCR7 from indirect co-enrichment via the complex
   • No binding site on QCR7 identified
   • No functional consequence of probe engagement demonstrated
3. 2025 Medium

   Whether QCR7 responds to atovaquone, the canonical Complex III inhibitor, was untested; solvent proteome profiling showed QCR7 is stabilised by atovaquone treatment.

   Evidence Solvent-induced proteome profiling (differential protein stability by mass spectrometry) comparing atovaquone vs. DMSO in P. falciparum lysates

   PMID:41308470

   Open questions at the time

   • Single lab, single proteomics method; stabilisation reflects complex association rather than a direct QCR7 drug-binding role
   • Does not define whether QCR7 contributes to atovaquone sensitivity or resistance
   • No mechanistic link between stabilisation and QCR7 function

• The intrinsic molecular function of QCR7 within Complex III, its direct interaction partners, and any independent contribution to electron transfer or complex assembly remain undefined.
• No catalytic activity or biochemical role assigned to QCR7 itself
• No direct binding mechanism to any inhibitor established for QCR7
• No genetic knockdown/knockout phenotype characterized for QCR7 in the corpus