A malaria parasite (green/purple structure) invades a red blood cell. Image credit: Ryan Kissinger, Visual Medical Arts Department, Rocky Mountain Labs, NIAID (CC BY 4.0)
Malaria is an infectious disease caused by the family of Plasmodium parasites, which pass between mosquitoes and animals to complete their life cycle. With one bite, mosquitoes can deposit up to one hundred malaria parasites into the human skin, from where they enter the bloodstream. After increasing their numbers in liver cells, the parasites hijack, invade and remodel red blood cells to create a safe space to grow and mature. This includes inserting holes in the membrane of red blood cells to take up nutrients from the bloodstream.
A complex of three tightly bound RhopH proteins plays an important role in these processes. These proteins are unique to malaria parasites, and so far, it has been unclear how they collaborate to perform these specialist roles.
Here, Schureck et al. have purified the RhopH complex from Plasmodium-infected human blood to determine its structure and reveal how it moves within an infected red blood cell. Using cryo-electron microscopy to visualise the assembly in fine detail, Schureck et al. showed that the three proteins bind tightly to each other over large areas using multiple anchor points. As the three proteins are produced, they assemble into a complex that remains dissolved and free of parasite membranes until the proteins have been delivered to their target red blood cells. Some hours after delivery, specific sections of the RhopH complex are inserted into the red blood cell membrane to produce pores that allow them to take up nutrients and to grow.
The study of Schureck et al. provides important new insights into how the RhopH complex serves multiple roles during Plasmodium infection of human red blood cells. The findings provide a framework for the development of effective antimalarial treatments that target RhopH proteins to block red blood cell invasion and nutrient uptake.
