The study provides details that will help scientists design better vaccines and drug treatments for the strain, Plasmodium vivax.
"More people live at risk of infection by this strain of malaria than any other," said senior author Niraj Tolia, PhD, assistant professor of molecular microbiology and of biochemistry and molecular biophysics. "We now are using what we have learned to create vaccines tailored to stop the infectious process by preventing the parasite from attaching to red blood cells."
The finding appears Jan. 9 in PLOS Pathogens.
The World Health Organization estimates there were more than 200 million malaria cases in 2012. The deadliest form of malaria, Plasmodium falciparum, is most prevalent in Africa. But P. vivax can hide in the liver, re-emerging years later to trigger new infections, and is harder to prevent, diagnose and treat.
Earlier studies had suggested that one P. vivax protein binds to one protein on the surface of red blood cells. Tolia's new study reveals that the binding is a two-step process that involves two copies of a parasite protein coming together like tongs around two copies of a host protein.
"It's a very intricate and chemically strong interaction that was not easily understood before," Tolia said. "We have had hints that other forms of malaria, including the African strain, may be binding in a similar fashion to host cells, but this is one of the first definitive proofs of this kind of attack."
Tolia suspects blocking any of the proteins with drugs or vaccines will stop the infectious process.
"For example, some people have a mutation that eliminates the protein on red blood cell surfaces that P. vivax binds to, and they tend to be resistant to the parasite," he said. "This is why this strain isn't prevalent in Africa — evolutionary pressure has caused most of the populations there to stop making this protein."
Tolia also found evidence that other people with immunity to P. vivax have developed naturally occurring antibodies that attach to a key part of the parasite's binding protein, preventing infection.
"The parasite protein is very large, and human antibodies bind to it at many different points along its length," Tolia explained. "We have observed that the ones that are most effective so far are the antibodies that bind to the protein at the region highlighted by our new research."
This research was made possible by funding from the National Institute for Allergy and Infectious Diseases of the National Institutes of Health (NIH) (R01 080792), the Edward Mallinckrodt, Jr. Foundation, an American Heart Association postdoctoral fellowship, and a National Science Foundation Graduate Research Fellowship (DGE-1143954).
Batchelor JD, Malpede BM, Omattage NS, DeKoster GT, Heinzler-Wildman KA, Tolia NH. Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC. PLOS Pathogens, online Jan. 9, 2014.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Michael C. Purdy | EurekAlert!
Uncuffing nitric oxide production: Beta-arrestin2 complexes regulate NO levels
05.06.2020 | Medical University of South Carolina
Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Humans rely dominantly on their eyesight. Losing vision means not being able to read, recognize faces or find objects. Macular degeneration is one of the major...
In meningococci, the RNA-binding protein ProQ plays a major role. Together with RNA molecules, it regulates processes that are important for pathogenic properties of the bacteria.
Meningococci are bacteria that can cause life-threatening meningitis and sepsis. These pathogens use a small protein with a large impact: The RNA-binding...
An analysis of more than 200,000 spiral galaxies has revealed unexpected links between spin directions of galaxies, and the structure formed by these links...
Two prominent X-ray emission lines of highly charged iron have puzzled astrophysicists for decades: their measured and calculated brightness ratios always disagree. This hinders good determinations of plasma temperatures and densities. New, careful high-precision measurements, together with top-level calculations now exclude all hitherto proposed explanations for this discrepancy, and thus deepen the problem.
Hot astrophysical plasmas fill the intergalactic space, and brightly shine in stellar coronae, active galactic nuclei, and supernova remnants. They contain...
In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".
Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
05.06.2020 | Life Sciences
05.06.2020 | Physics and Astronomy
05.06.2020 | Life Sciences