SSRL | Highlights Archive | Headlines | Publications | User Resources | SLAC | Stanford University

Scientific Highlight
W.G.J. Hol Research


31 January 2007

  Key Component of Malaria Parasite Invasion Motor Revealed

summary written by Alison Drain, SLAC Communication Office


Researchers from the University of Washington working at SSRL have solved the structure of a protein complex that may one day be exploited to combat drug-resistant strands of the parasite that causes malaria, Plasmodium. Malaria, one of the most devastating diseases worldwide, infects 300 to 500 million people and causes about 2 million deaths each year.

The x-ray crystallography experiments, performed at SSRL beam line 9-2 and at the Advanced Light Source in Berkeley, California, provide atomic-level insights into a crucial interaction occurring in a multi-protein assembly found in the invasion machinery of the malaria parasite. A multi-protein complex located between the parasite's plasma membrane and inner membrane complex empowers the parasite Plasmodium to move and invade a host cell. This complex is required for the parasite to enter and leave different types of host cells and is highly conserved among Plasmodium variants.

The group solved the structure of a complex of Myosin A tail interacting protein (MTIP) and MyoA-tail to 2.6 . The crystallized samples used contained three different conformations of MTIP in one single crystal, which allowed the scientists to assess the protein's crucial interaction with the MyoA-tail by comparing three independent subunits. MTIP bridges between the membranes associated proteins and the tail of myosin, which interacts with short actin filaments. The actin filaments are attached to the enzyme aldolase, which connects actin and Thrombospondin Anonymous Repeat Protein (TRAP), which initiates the process of invasion.

The researchers performed inhibition experiments with MyoA-tail to test the viability of P. falciparum, a dangerous malaria-causing Plasmodium species. Because the MyoA-tail interacting P. falciparum MTIP residues differ significantly from the human homolog, structure-based drug design can exploit this feature and may hold promise for new therapies to combat malaria infection. The results were published in the March 28, 2006 edition of the Proceedings of the National Academy of Sciences.

To learn more about this research see the full scientific highlight at:

Bosch, J., Turley, S., Daly, T. M., Bogh, S. M., Villasmil, M. L., Roach, C., Zhou, N., Morrisey, J. M., Vaidya, A. B., Bergman, L. W., et al. (2006). Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor. Proc. Natl. Acad. Sci. U. S. A. 103, 4852-4857