Plasmodium falciparum 6-cysteine protein P52 and Plasmodium falciparum 6-cysteine protein P36 (P52 and P36)

Plasmodium falciparum P52 and P36 are two paralogous proteins classified in the 6-cysteine (s48/45) domain family, encoded by contiguous genes on chromosome 4. They are expressed in the sporozoite stage and localize to the micronemes, facilitating the invasion of hepatocytes during the liver stage of malaria infection. P52 is GPI-anchored, while P36 is membrane-associated and forms a complex with P52 within sporozoites. Both are essential for the formation of the parasitophorous vacuole membrane (PVM), a structure required for successful establishment of the liver-stage infection. P36 directly mediates interactions with host hepatocyte receptors such as EphA2, CD81, and SR-B1, while P52 acts in concert with P36 to enable productive infection. Knockout of these genes results in attenuated parasites unable to develop in the liver, providing the basis for genetically attenuated parasite vaccines that have advanced to early clinical trials. No drugs are currently known to target these proteins directly, but their immunogenic properties and essential roles in the liver stage make them key research and clinical vaccine targets for malaria control.

Other names

PfP52 (PlasmoDB: PFD0215c, GenBank: XP_001351357)PfP36 (PlasmoDB: PFD0210c, GenBank: XP_001351356)Micronemal protein P52Micronemal protein P366-cysteine domain proteins

Genetic deletion disrupts sporozoite ability to invade hepatocytes, preventing liver-stage development of malaria parasite (attenuation for vaccine). Antibodies against these proteins can inhibit sporozoite invasion/traversal of hepatocytes. No direct pharmacological modulators (e.g., inhibitors or activators) known.