1. Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes
- Author
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Alan F. Cowman, Brian J. Smith, Julie Healer, Jenny Thompson, Yibin Xu, Michael C. Lawrence, and Lin Chen
- Subjects
Erythrocytes ,QH301-705.5 ,Science ,Plasmodium falciparum ,Short Report ,malaria ,Biology ,Crystallography, X-Ray ,Ligands ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,parasitic diseases ,medicine ,Parasite hosting ,Humans ,human ,Biology (General) ,030304 developmental biology ,0303 health sciences ,Microbiology and Infectious Disease ,General Immunology and Microbiology ,General Neuroscience ,Liver cell ,030302 biochemistry & molecular biology ,General Medicine ,medicine.disease ,biology.organism_classification ,Biophysics and Structural Biology ,invasion ,Virology ,Recombinant Proteins ,3. Good health ,plasmodium ,Infectious disease (medical specialty) ,Basigin ,biology.protein ,Medicine ,Mutant Proteins ,erythrocyte ,Antibody ,Carrier Proteins ,Malaria ,Protein Binding - Abstract
Plasmodium falciparum causes the most severe form of malaria in humans and is responsible for over 700,000 deaths annually. It is an obligate intracellular parasite and invades erythrocytes where it grows in a relatively protected niche. Invasion of erythrocytes is essential for parasite survival and this involves interplay of multiple protein–protein interactions. One of the most important interactions is binding of parasite invasion ligand families EBLs and PfRhs to host receptors on the surface of erythrocytes. PfRh5 is the only essential invasion ligand within the PfRh family and is an important vaccine candidate. PfRh5 binds the host receptor basigin. In this study, we have determined the crystal structure of PfRh5 using diffraction data to 2.18 Å resolution. PfRh5 exhibits a novel fold, comprising nine mostly anti-parallel α-helices encasing an N-terminal β-hairpin, with the overall shape being an elliptical disk. This is the first three-dimensional structure determined for the PfRh family of proteins. DOI: http://dx.doi.org/10.7554/eLife.04187.001, eLife digest Malaria is a disease caused by a single-celled parasite called Plasmodium, which is transmitted between humans by mosquitoes. It is estimated that 3.4 billion people worldwide live in regions where they are at risk of malaria, and malaria infections cause hundreds of thousands of deaths each year. When a mosquito carrying Plasmodium parasites in its salivary glands bites a human, the parasite is injected into the person's bloodstream with the mosquito's saliva. The parasite then travels through the bloodstream to the liver, where it infects liver cells and multiplies without causing any symptoms for up to 4 weeks. After this period, the parasites break out of each infected liver cell, re-enter the bloodstream, and begin infecting red blood cells. When another mosquito bites the infected individual to feed on their blood, the parasite moves into the mosquito with the red blood cells and the cycle of infection continues. While prevention and control measures have dramatically reduced the incidence of malaria in some countries, many people in African countries—and especially young children—die from malaria each year. Finding ways to reduce the spread of Plasmodium parasites, and in particular Plasmodium falciparum (which is responsible for the deadliest type of malaria), is critical for the global effort to control and eliminate this disease. As such, many researchers are trying to gain a better understanding of how the parasite both invades host cells and evades the immune system. In this study, Chen et al. reveal the high-resolution structure of PfRh5, the protein from Plasmodium falciparum that forms a complex with other proteins to allow the parasite to bind to, and invade, red blood cells. This is one of the first three-dimensional structures that have been uncovered for this family of proteins—and reveals that the PfRh5 protein is shaped like an elliptical disk. Solving the structure of PfRh5 is the first step in understanding the role of this protein, and the other protein components, involved in invading red blood cells. These proteins are molecules that could potentially be used to vaccinate people against malaria, and understanding these proteins' functions will help efforts to design vaccines to prevent malarial disease. DOI: http://dx.doi.org/10.7554/eLife.04187.002
- Published
- 2014