21/12/05

‘Key’ allowing malaria into human cells described

Two Plasmodium vivax parasites inside a red blood cell Copyright: CDC / Steven Glenn, Laboratory & Consultation Division

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[JINAN] Atom by atom, scientists have discovered the shape of a key part of a protein that malaria parasites use to invade human red blood cells.


The study, published online by Nature today (21 December), focused on Plasmodium knowlesi, a strain of malaria that usually infects monkeys rather than people.


But its authors say their findings could help researchers develop new drugs against Plasmodium vivax, a malaria parasite that infects millions of people each year and attacks red blood cells in the same way as P. knowlesi.


Malaria parasites replicate inside these blood cells. To get inside, they use a protein on their surface to latch onto a protein on the outside of the blood cell (see Malaria parasite’s ‘secret handshake’ revealed).


The most important part of the parasite’s protein is the ‘Duffy-binding-like domain’. Until now, its structure was not clear.


The researchers, from the India-based International Centre for Genetic Engineering and Biotechnology (ICGEB) and a French unit of the European Molecular Biology Laboratory, have now pinpointed the three-dimensional position of each of the domain’s atoms using a technique called X-ray crystallography.


Knowing this should allow researchers to “find weak points that could make good targets for drugs”, says lead author Amit Sharma of the ICGEB.


P. vivax is the commonest and most widespread malaria parasite, infecting 80 million people a year. Although it causes a debilitating disease, it is rarely fatal, unlike Plasmodium falciparum, which kills more than a million people a year in Africa.


P. falciparum invades human blood cells using proteins similar to those of P. vivax and P. knowlesi. The current research may have fewer implications for tackling this more deadly strain, however, as P. falciparum binds to different proteins on human blood cells.



Reference: Nature (2005) doi:10.1038/nature04443