Structure and interactions of Mycobacterium tuberculosis Mce-associated membrane (Mam) and orphaned Mam (Omam) proteins

Tuberculosis (TB) is a human respiratory infection caused by the bacterium, Mycobacterium tuberculosis (Mtb). The disease affects approximately 11 million people kills 1.2 million each year. In the recent years, both the number of people affected by TB and the number of strains of the bacteria that are resistant to drugs have been increasing. TB remains a difficult disease to treat, as Mtb has developed ways to survive inside human cells. One important nutrient for Mtb is the fats and carbon compounds stored in human cells. Mtb has various mechanisms to deprive these nutrients from human cells and use them for its own survival.
Mtb has four so-called mammalian cell entry protein (Mce) complexes, which bring fat-based nutrients to Mtb from human cells. This dissertation focuses on two families of Mce accessory proteins, the Mce-associated (Mam) proteins and the orphan Mam (Omam) proteins.
The dissertation focuses on the Mam proteins of the Mce1 complex, and in particular on the Mam1A protein. Experiments revealed that Mam1A independently forms a cluster of four proteins that is stabilized by the internal sulfur bonds between the two Mam1A proteins. In addition, the Mam1ABCD proteins form a larger complex, which was also found to include the lipid uptake-coordinating protein, LucA.
Another major research topic of the dissertation is the OmamC protein, and in particular, to investigate its interactions with other proteins. The interaction study revealed that OmamC is somehow important in many different energy metabolic pathways. In addition, the structure of OmamC was successfully determined using crystallization methods. The structure of OmamC is the first structure of the protein family to be determined, which will help us understand their function and possibly develop new drugs against TB.