COX11

PF3D7_1475300 (COX11) is a copper-binding protein of Plasmodium falciparum whose C-terminal domain binds copper in vitro, as established through complementary biochemical assays including bicinchoninic acid release, atomic absorption spectroscopy, and thermal shift analysis (PMID:35672733). Site-directed mutagenesis localized this copper-binding activity to cysteine 157, whereas cysteine 60 was dispensable (PMID:35672733). The native protein is expressed in P. falciparum, confirmed by antibodies raised against the recombinant C-terminal domain (PMID:35672733). Beyond in vitro copper binding by its C-terminal domain and confirmation of native expression, no further mechanistic detail — including in-parasite function, copper-transfer activity, or interaction with cytochrome c oxidase — has been characterized in the available corpus.

1. 2022 Medium

   To test whether P. falciparum COX11 functions as a copper-binding protein, its recombinant C-terminal domain was assayed for copper binding, establishing a metal-binding activity attributable to a specific cysteine residue.

   Evidence Recombinant expression with multiple in vitro copper-binding assays (BCA release, atomic absorption spectroscopy, thermal shift) and cysteine mutagenesis

   PMID:35672733

   Open questions at the time

   • No structural model of the copper-binding site
   • No demonstration that copper is transferred to cytochrome c oxidase or the CuB site
   • No in-parasite functional rescue or knockout to confirm physiological role
2. 2022 Medium

   To confirm that COX11 is more than a predicted open reading frame, antibodies against the recombinant C-terminal domain detected the native protein, establishing that COX11 is expressed in the parasite.

   Evidence Immunodetection of native protein using polyclonal antibodies raised against recombinant C-terminal domain

   PMID:35672733

   Open questions at the time

   • Single immunodetection method without subcellular localization data
   • Stage-specific expression not characterized
   • Mitochondrial localization not experimentally demonstrated

• Whether COX11 transfers copper to cytochrome c oxidase in the parasite mitochondrion and is required for parasite viability remains unresolved.
• No in-parasite functional or genetic evidence
• No demonstrated interaction with cytochrome c oxidase
• No copper-transfer reconstitution