Malaria causing Plasmodium parasites have developed an elaborate protein trafficking pathway to facilitate the export of hundreds of its effector proteins into their host cell, the erythrocyte. These exported proteins mediate the structural remodelling of the erythrocyte which is crucial for the parasite’s virulence as well as facilitating its survival and growth. To reach the host cell cytosol, parasite protein export requires the translocation across a double-encasing membrane, the parasite plasma membrane (PPM) and the parasitophorous vacuole membrane (PVM) via a complex termed the Plasmodium translocon of exported proteins (PTEX). When perturbed by gene knock-out or conditional knock-down of core components in PTEX, it results in a dramatic reduction and blockage of protein trafficking and ultimately subsequent parasite death.
Through biochemical and proteomic approaches, we examine the function of an individual core PTEX component, HSP101 in both human and rodent malaria parasites. HSP101 is a AAA+-ATPases which comprise of ring-shaped hexamers and believed to be the motor source providing energy for cargo unfolding and driving proteins through the central pore. By affecting the structure of HSP101 and therefore how it interacts with the other PTEX components, we assess its physical role in the complex and how these modifications affect cargo export. These findings have given insight into the mode of action of PTEX and has led to further understanding of how endogenous protein export is mediated by the parasite. Importantly, this study further highlights PTEX as an excellent drug target for future anti-malarial development.