Journal article:: www.nature.com/articles/s4158...
Print article: bit.ly/ptex-protein
Malaria is a serious global health issue, and a leading cause of death and disease in developing countries. This life-threatening infectious disease is caused by Plasmodium parasites, which are transmitted between humans by mosquitoes. In recent years, the search for new anti-malarial drugs has become increasingly urgent, due to the rise of malaria parasites that are resistant to the currently available treatments. Malaria parasites make humans sick by invading/infecting and reproducing inside human red blood cells. In order to design new anti-malarial drugs, we have to build a better understanding of how the parasites are able to enter and live inside our red blood cells. To do this, we decided to learn more about a very important malarial molecular machine made of proteins, called PTEX (the Plasmodium Translocon of Exported Proteins).
Normal human red blood cells are too simple to provide enough nutrients to support actively growing parasites. When a parasite enters a red blood cell, the parasite takes part of the red blood cell membrane to build a protective compartment around it, called a vacuole. The parasite then produces hundreds of malarial ‘effector’ proteins, and uses PTEX to transport the effector proteins out of the vacuole so they can remodel the red blood cell into a new home for the parasite. To learn exactly how PTEX works, we extracted PTEX from malaria parasites and used a method called cryoEM to obtain high resolution 3D-structures of this molecular machine in action. These structures help us to understand how this unique machine works at the atomic level. From these structures, we can see how PTEX unfolds hundreds of malarial proteins and transports them across the vacuole membrane, into the red blood cell. This new understanding of this fascinating molecular machine paves the way for designing desperately needed new anti-malarial drugs.
CNSI:
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EICN:
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MBI:
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Chi-Min Ho (Lead author):
/ mimi1inh