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Researchers Discover Protein That Causes Malaria

Researchers have discovered the protein that enables the malaria parasites to attack the red blood cells. The research findings, which were published in the journal Cell, will help the scientists in designing vaccines against the dreaded disease of malaria.//

A major pathway through which malaria parasites invade red blood cells is the binding of a protein on the surface of merozoites called EBA-175 to a receptor protein on the surface of red blood cells called glycophorin A. Merozoites die if they do not invade red blood cells soon after their release (from liver cells) into the bloodstream. Thus, the binding of EBA-175 to glycophorin A is a prominent target for the development of therapies to control malaria.

To explore the molecular basis of the binding of EBA-175 to glycophorin A—with the rationale that such information might reveal strategies for preventing and treating malaria—the researchers used x-ray crystallography to determine the atomic structure of a key portion of the EBA-175 protein called the RII domain.

The results revealed that two molecules of RII come together in a manner resembling a handshake, and that the overall shape of such RII "dimers" resembles a donut with two holes. Next, to identify precisely which parts of the RII surface bind to glycophorin A, the researchers determined the atomic structure of RII crystallized along with sugar molecules called glycans. Glycans displayed on the glycophorin A receptor are required for RII binding and for the invasion of red blood cells by the malaria parasite.

The new results finding suggested that the RII handshake interaction serves to clamp the parasite protein onto the glycophorin A receptor of red blood cells. An important idea stemming from this view is that blocking the RII interaction—with drugs or vaccines—should block glycophorin A receptor binding and forestall malaria infection.

To test this idea, the researchers created altered versions of the
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