A major virulence determinant in the protozoan parasite Plasmodium falciparum is a protein complex known as PTEX (Plasmodium Translocon of EXported proteins). PTEX is a putative protein trafficking machinary responsible for the export of hundreds of proteins across the parasitophorous vacuole membrane and into the human host cell. Five proteins are known to comprise the PTEX complex and in this study, three of the major stoichiometric components are investigated including; HSP101 (a AAA+ ATPase); a protein of no known function termed PTEX150; and the apparent membrane component EXP2. We show that these proteins are synthesized in the preceding schizont-stage (PTEX150 and HSP101), or even earlier in the life-cycle (EXP2) and prior to invasion these components reside within the dense granules of invasive merozoites, From these apical organelles, the protein complex is released into the host cell where it resides with little turnover in the parasitophorous vacuole membrane for most of the remainder of the following cell cycle. At this membrane, PTEX is arranged in a stable macromolecular complex of >1230kDa which includes a ~600 kDa apparently homo-oligomeric complex of EXP2, that can be separated from the remainder of the PTEX complex using non-ionic detergents. Two different biochemical methods undertaken here suggest that PTEX components are arranged in the order of EXP2-PTEX150-HSP101, with EXP2 associating with the vacuolar membrane. Collectively, these data support the hypothesis that EXP2 oligomerises and potentially forms the putative membrane-spanning pore to which the remainder of the PTEX complex is attached.
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