The parasite that causes malaria invades and prospers in various tissues such as skin, blood, liver, gut, and salivary glands of its human and mosquito hosts. The invasion of many different kinds of cells implies that the parasite makes use of a diverse cell biology of receptor-ligand interactions. By determining the three-dimensional structures of receptor and ligand proteins, we are studying the interactions that allow the parasite to specifically target a particular type of cell to invade. The parasite receptors, being on the cell surface, are also prime candidates for the development of anti-malarial vaccines as immunity to malaria appears to correlate with immune responses to cell surface receptors. We have crystallized three malarial cell surface proteins and are working on several more. With x-ray diffraction data in hand for two receptors, we are proceeding to determine their three-dimensional structures. We have obtained x-ray data and are seeking improved crystals and data for two additional receptors. The receptors we are studying are candidates for inclusion in a vaccine and are expressed in several life stages of the malarial parasite. Through these studies we expect to reveal the overall shapes and the specific interactions of important receptors on the parasite.
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