The parasite Plasmodium falciparum, a causative agent of malaria, infects red blood cells in humans. (Source: National Institute of Allergy and Infectious Diseases (NIAID)/Rocky Mountain Laboratory - Research.gov)

The parasite Plasmodium falciparum, a causative agent of malaria, infects red blood cells in humans. (Source: National Institute of Allergy and Infectious Diseases (NIAID)/Rocky Mountain Laboratory)

Malaria is a fever-based illness that has been a major issue across the globe, particularly in Africa. The history of malaria stretches back to prehistoric origins and is still a widespread and often lethal disease in the 21st century. Recently, however, scientists at the Okinawa Institute of Science and Technology (OIST) have gained information that may be useful in combating malaria (1).

Malaria is caused by the parasite Plasmodium falciparum, which attacks red blood cells (1). After maturing in the liver, the parasite begins its attack, infecting red blood cells, causing them to burst and allowing them to then infect nearby cells (1). Ironically, this behavior is facilitated by immune mechanisms of the body meant to fight the disease itself (1).

PfEMP1, a protein found in Plasmodium, sticks out of the red blood cells and binds to immunoglobulin M (IgM), which would normally work to fight malaria (1). IgM is a type of antibody, critical proteins in the immune system that identify and fight foreign pathogens.

The binding of IgM causes Plasmodium to spread because the complex formed between the PfEMP1 and IgM attracts other red blood cells (1). This close proximity of red blood cells makes it easier for the parasite to jump from cell to cell. In addition, the resulting cluster of cells can clog capillaries, causing the fever symptoms often seen in malaria (1).

In addition, PfEMP1 blocks the IgM’s binding site for C1q (2). This protein, C1q, is a major part of the membrane attack complex, a means of killing infected cells. Thus PfEMP1 effectively halts the immune response to Plasmodium. The scientists at OIST, in hopes of solving these problems, studied the structural causation for the functions of PfEMP1.

Employing a number of methods, the OIST researchers pieced together 3D models of both PfEMP1 and IgM (2). Methods of viewing the proteins varied from staining to cryogenic freezing to electron tomography. (2). Electron tomography refers to the use of electron microscope technology for the collection of data. In order to construct the 3D models, images had to be taken at many different angles (2).

The researchers found that PfEMP1 has a rigid, C-shaped configuration, while IgM has three different configurations, all relatively C-shaped (2). Professor Ulf Skoglund, the head of the team, states that this allows for a bond between the proteins that is not too loose or too strong, and is perfect for undermining the human immune system (1).

In the future, there will be a great amount of use for this research. Knowledge of PfEMP1 structure should allow for the development of pharmacological treatments that counteract the protein (1).

References:

  1. Okinawa Institute of Science and Technology Graduate University – OIST. (2016). How malaria fools our immune system. ScienceDaily. Retrieved from sciencedaily.com/releases/2016/01/160114121913.htm
  2. Akhouri, R. R., Goel, S., Furusho, H., Skoglund, U., & Whalgren, M. (2016). Architecture of human IgM in complex with P. falciparum erythrocyte membrane protein 1. Cell Reports, 14(4), 723-736. doi: 1016/j.celrep.2015.12.067