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.
AdvertisementTo 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 RII protein that they predicted would block the RII handshake, glycan binding, or both. The result: All such altered versions of the RII protein failed to bind to red blood cells, confirming the idea that drugs or vaccines that block the RII interaction, glycan binding, or both might be effective therapies for malaria.
The research reports will enable researchers to design very specific treatments for the disease. The EBA-175 protein and others related to it appear to be unique to Plasmodium, so they are excellent drug and vaccine targets, reported the researchers.
Medindia on Malaria: Further information
Malaria: Malaria is a disease caused by parasites and is spread by the mosquitoes that bite an infected person and goes on to bite a healthy person and pass on the infection. Fever, headache, vomiting and other flu like symptoms characterize the condition. The malaria attack if not treated on time can be life threatening to the patient.
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