Speaker: Josh Beck, Assistant Professor - Biomedical Sciences, Iowa State University
Title: Mechanism of Malaria parasite effector protein export to hijack the host cell
Abstract: Intraerythrocytic malaria parasites reside within a vacuole membrane generated during host cell invasion. To establish their intracellular niche and remodel their host cells, these parasites deliver an array of effector proteins across this membrane barrier into the host compartment. This process depends on the Plasmodium translocon of exported proteins (PTEX) consisting of three core proteins including the AAA+ ATPase HSP101 and two additional proteins known as PTEX150 and EXP2. In a recent collaborative effort, we determined the structure of the PTEX core complex at near atomic resolution using cryo-electron microscopy, revealing PTEX as a bone fide translocon machine with the HSP101 unfoldase coupled to the EXP2 membrane-spanning pore by a flange formed by PTEX150. Surprisingly, the EXP2 membrane pore was also found to function as a small molecule channel to facilitate nutrient passage across the vacuole independent of HSP101. This small molecule channel activity appears to have preceded the translocon function, providing a unique evolutionary snapshot of the adaptation of a membrane pore to diverse functions. Collectively, our work reveals the mechanism of key transport process at the vacuole membrane and provides a starting point for rational drug discover to target these essential parasite processes.