Malaria is an infectious disease that is transmitted to people through the bite of mosquitoes infected with Plasmodium. It affects more than 200 million people each year and kills nearly half a million people each year. When bitten by a mosquito, the Plasmodium invades human erythrocytes, acquires a portion of the erythrocyte membrane, and forms a protective compartment around it, known as a vacuole.
Normal red blood cells are too simple to provide enough nutrients to support actively growing Plasmodium. Every Plasmodium that invades red blood cells is like living in an empty warehouse, and hundreds of Plasmodium “effect” proteins must be produced to reshape red blood cells into a home suitable for growth. Plasmodium translocon of exported proteins (PTEX) are protein complexes that transport these malaria parasite proteins into red blood cells. PTEX acts as a guard; without it, these effector proteins are trapped in the vacuole. But so far, scientists don’t know how PTEX is involved in transporting these proteins to red blood cells.
In a new study, researchers from the University of California, Los Angeles, and the Medicine School of the University of Washington used human blood to culture Plasmodium in the laboratory. They extracted PTEX from these malaria parasites and quickly frozen it at minus 190℃. They used a technique called cryoelectron (cryoEM) to obtain pictures of PTEX particles. Therefore, for the first time, they resolved the structure of PTEX at the atomic level. They found that PTEX is made up of three proteins that act as molecular machines. The relevant research results were published online in Nature, and the title is “Malaria parasite translocon structure and mechanism of effector export”. The corresponding author of the paper is Z. Hong Zhou and Pascal F. Egea of the University of California, Los Angeles. The first author of the paper is Chi-Min Ho of the University of California, Los Angeles.
The first protein in PTEX is the engine that drives protein transport; it unfolds these Plasmodium effector proteins and lets them pass through the remaining two proteins in PTEX. A protein in the middle is like an adapter that connects the engine to the last protein that resembles a funnel in shape, allowing the transport of these effector proteins into red blood cells.
Ho said, “When we collect malaria parasites, they are at a specific moment in their life cycle, at which point they actively transport these effector proteins into red blood cells. We are happy to find that unfolded proteins are trapped inside PTEX, and this indicates that PTEX is directly responsible for transporting these effector proteins.”
These researchers hope that their findings may help promote the development of new drugs that target PTEX and prevent it from functioning properly.
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Reference
Ho CM, Beck JR, Lai M, et al. Malaria parasite translocon structure and mechanism of effector export. Nature. 2018 Sep;561(7721):70-75. doi: 10.1038/s41586-018-0469-4.