Family members stick together: multi-protein complexes of malaria parasites

Malaria parasites express a broad repertoire of proteins whose expression is tightly regulated depending on the life-cycle stage of the parasite and the environment of target organs in the respective host. Transmission of malaria parasites from the human to the anopheline mosquito is mediated by intraerythrocytic sexual stages, termed gametocytes, which circulate in the peripheral blood and are essential for the spread of the tropical disease. In Plasmodium falciparum, gametocytes express numerous extracellular proteins with adhesive motifs, which might mediate important interactions during transmission. Among these is a family of six secreted proteins with adhesive modules, termed PfCCp proteins, which are highly conserved throughout the apicomplexan clade. In P. falciparum, the proteins are expressed in the parasitophorous vacuole of gametocytes and are subsequently exposed on the surface of macrogametes during parasite reproduction in the mosquito midgut. One characteristic of the family is a co-dependent expression, such that loss of all six proteins occurs if expression of one member is disrupted via gene knockout. The six PfCCp proteins interact by adhesion domain-mediated binding and thus form complexes on the sexual stage surface having adhesive properties. To date, the PfCCp proteins represent the only protein family of the malaria parasite sexual stages that assembles to multimeric complexes, and only a small number of such protein complexes have so far been identified in other life-cycle stages of the parasite.