Malaria knot loosens up a little

New Delhi, Dec. 21: Indian biologists today announced that they have caught the first glimpses of the molecular machinery that the malaria parasite Plasmodium vivax uses to invade human red blood cells.

Biophysicist Amit Sharma at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi and his colleagues have unravelled the detailed 3D structure of a key protein that the parasite uses to enter red blood cells.

While the Plasmodium parasite slips into the bloodstream through mosquito bites, scientists have known for nearly two decades that it uses a protein called the Duffy Binding Protein to enter human red blood cells. Inside the blood cells, the parasite multiplies over several days, eventually causing the cells to burst which leads to fever and chills, the hallmark symptoms of malaria.

“But until now no one really knew what this protein looked like,” said Virander Chauhan, director of the ICGEB. “The exact shape of the protein is important to understand the process of entry as well as to find ways to block the process,” he said.

In a study published in this week’s edition of the journal Nature, the ICGEB team has described the structure of the protein. Scientists believe this work could serve as an advance towards finding new drugs against malaria.

Plasmodium vivax currently accounts for about 60 per cent of the estimated 1.8 million annual cases of malaria in India. The others are caused by Plasmodium falciparum, a far more lethal organism that can lead to cerebral malaria.

Sharma and his colleagues produced tiny crystals of the protein at the ICGEB and then borrowed time at an X-ray beam facility at a European laboratory in Grenoble, France, to generate 360 X-ray images and study the protein crystals.

The scientists used X-ray crystallography to create atom-by-atom images of proteins too small to be seen under microscopes. “It was a tricky molecule. It was difficult to make the protein in its crystal form for biological studies,” Sharma told The Telegraph.

Until the ICGEB researchers developed crystals and the X-ray images, no one had ever had close-up views of the exact surface that the parasite’s protein uses to interact with human red blood cells.

Scientists believe that detailed knowledge of the protein’s structure could be used to design new drugs. The parasite uses the Duffy protein to recognise a specific molecule on the red blood cell that it uses as a gateway for entry.

“One possible goal of future research would be to find a candidate drug molecule that might interfere with this recognition process,” Sharma said.

A scientist at the European Molecular Biology Laboratory who collaborated with the ICGEB team on X-ray imaging studies said the Duffy protein has a unique architecture. “So there should be a way to inhibit its activity without affecting healthy blood cells,” said Hassan Beirhali, the collaborating scientist.

Among several species of Plasmodium, the ICGEB team worked with a species that does not easily infect humans. But Duffy proteins are similar in different Plasmodium species, making it likely that the findings may also apply to other types of Plasmodium.