Plasmodium invades the body’s young red blood cells, which then begin to spread throughout the body. In a new study, researchers from Australia and the United States used cryo-electron microscopy (cryo-EM) to reveal for the first time at the atomic level a three-dimensional picture of how Plasmodium vivax invades human red blood cells. They mapped out the first contact between the Plasmodium and the young red blood cells they are invading, cracking the molecular machinery they use to attach to human red blood cells—three-dimensional structure of a ternary invading complex formed by the combination of P. vivax protein PvRBP2b and human transferrin receptor 1 (TfR1) and transferrin. This is an important step in the development of a new malaria vaccine. The results of the study were published online in Nature, entitled “Cryo-EM structure of an essential Plasmodium vivax invasion complex”. The author of the paper is Dr. Zhiheng Yu, a researcher at the Howard Hughes Medical Institute in the United States, and Dr. Wai-Hong Tham from the Walter-Eliza-Hall Medical Institute in Australia. The first author of the paper is Dr. Jakub Gruszczyk of the Walter-Eliza-Hall Institute of Medicine and Dr. Rick Huang of the Howard Hughes Medical Institute.

 

 

Earlier this year, in a study published in Science, these researchers have discovered that Plasmodium vivax invades human erythrocytes by hijacking human transferrin receptors. Now, with the help of revolutionary cryo-EM technology, they can visually observe the interaction between PvRBP2b and TfR1 and transferrin at the atomic level. This lays the foundation for the development of potential anti-malarial drugs and vaccines.

 

Plasmodium vivax is the most widely distributed malaria parasite in the world and is the leading cause of malaria in most countries outside Africa. Since it hides in the human liver and cannot be detected by the immune system, it is also the number one malaria parasite that causes recurrent malaria infection.

 

Under the guidance of this three-dimensional structure, researchers were able to resolve the exact details of this Plasmodium-host interaction and identify its most vulnerable sites.

 

“This is basically a design challenge,” Tham said, “P. vivax is very diverse, which is challenging for vaccine development. We have now identified this molecular machine, which will be the best target for developing antimalarial vaccines that are effective against a range of Plasmodium vivax. ”

 

“With this unprecedented detail, we are now able to begin designing new therapies that specifically target and destroy the ternary invading complex of this Plasmodium, and to prevent them from hijacking human red blood cells and spreading through the bloodstream, which ultimately prevents them from spreading to others.”

 

 

Reference

Jakub Gruszczyk, Rick K. Huang, Li-Jin Chan et al. Cryo-EM structure of an essential Plasmodium vivax invasion complex. Nature, Published online: 27 June 2018, doi:10.1038/s41586-018-0249-1