Ideal target for malaria therapy found

A new American research has discovered a protein produced by the malaria parasite that is central to its ability to take over human red blood cells.

The protein may now be used as an ideal target for malaria therapy.

The findings of the study, conducted by researchers at Washington University School of Medicine in St. Louis, have appeared in Nature.

Dan Goldberg, professor of medicine and molecular microbiology and a Howard Hughes Medical Institute Investigator, said: "The malaria parasite seizes control of and remodels the red blood cell by secreting hundreds of proteins once it's inside.
 
"But without this protein, plasmepsin V, those other proteins can't get out of the parasite into the blood cell, and the infectious process stops."

Goldberg had studied plasmepsin V earlier and knew it was a malarial protease or an enzyme that cuts other proteins. When another lab demonstrated that proteins essential to the infectious process were being clipped in a part of the parasite where Goldberg knew plasmepsin V was active, he and his colleagues speculated whether it was doing the clipping.

The proteins produced by the malaria parasite have a common segment or tag that plasmepsin V recognizes and acts on, clipping off part of the protein. Goldberg believes that on removal of the tag, the remainder of the protein binds to another protein that acts as a chaperone, bringing the proteins to a channel in the malaria parasite's outer membrane. The channel allows the protein to leave the parasite and enter the red blood cell.

Goldberg said: "There's a ticket-taker who greets you at the start and takes part of your ticket...That's plasmepsin V. He then hands you to an usher who gets you to your final destination."

In the test tube, parasites in which plasmepsin V had been disabled were not able to secrete the infectious proteins that allow them to commandeer red blood cells.

Goldberg pointed out: "This is the key enzyme that determines whether proteins get out to remodel the red blood cell or not, so it's a very attractive target for therapy...Another reason it's a good potential drug therapy target is that it doesn't vary much in different strains of malaria."