Structural and Functional Studies of Toxoplasma gondii Dynamin Related Protein B

Abstract

Caused by organisms in the Apicomplexa phylum, toxoplasmosis and malaria are parasitic diseases with significant global health impacts. An estimated 1 in every 3 individuals worldwide are infected with toxoplasmosis, and over 600,000 die annually from malaria. Apicomplexa are a group of single-celled parasites distinguished by specialized organelles in their apical region. Among these structures are micronemes and rhoptries, secretory organelles essential for host cell invasion. Though the process of microneme and rhoptry synthesis is not well understood, T. gondii Dynamin Related Protein B (TgDrpB) has been identified as a necessary component in their formation. While TgDrpB is implicated in the biogenesis pathway of micronemes and rhoptries, its structure and molecular mechanism are currently unknown. The goals for this project are therefore to investigate TgDrpB structure and mechanism in microneme and rhoptry synthesis. It is hypothesized that TgDrpB initiates the process of organelle biogenesis by budding vesicles from the Golgi, similar to that of human dynamin. Completion of this study will establish the structural basis by which TgDrpB accomplishes membrane fission necessary for the biogenesis of secretory organelles and that work to facilitate TgDrpB activity.