Untersuchung der Funktion der N-terminalen Verlängerung von GBP 130 von Plasmodium falciparum

The initial stages of the P. falciparum secretory pathway appear to be similar to that in higher eukaryotes, but with some important differences. It has been noted that, although many P. falciparum proteins contain so-called “canonical” signal peptides (with a central hydrophobic region, a hydrophilic N-region and a C-terminal region), a number of secreted proteins contain an unusual N-terminal region prior to the hydrophobic signal peptide (recessed signal peptides). These N-terminal sequences appear to target proteins to the ER, but how exactly this occurs, and the function of the extension remains unknown. For reasons that are currently not well understood, recessed signal sequences are found mostly attached to proteins predicted to be transported to the cytosol of the host erythrocyte. These proteins underlie the pathology of malaria infection, as they confer novel properties to the infected host cell. In this PhD thesis, we aim to dissect such unusual secretory signal peptides, with a view to understanding their function. We shall use several P. falciparum N-terminal regions to this end, including classical signal peptides, as well as proteins containing recessed hydrophobic domains.