Biophysical characterisation of the Plasmodium Falciparum GRASP analogues

Plasmodium falciparum is a unicellular eukaryotic parasite of human cells responsible for the majority of malaria cases. These mosquito borne parasites initially infect hepatocytes, where they reproduce for up to 10 days before inducing cell lysis and escaping into the bloodstream, where they proceed to infect erythrocytes. The infection of host cells by P. falciparum involves the secretion of many proteins into the host cytosol so as to alter its metabolic, structural and immune characteristics in a favorable manner. Golgi reassembly and stacking proteins (GRASPs) are a family of golgi associated proteins, first identified in humans, responsible for unconventional protein secretion in most eukaryotes, with the notable exception of plants. N. Struck et al identified two distinct GRASP analogues in P falciparum, while mammalian cells possess pairs of GRASPs, it is unusual for more than a single analogue to be present in lower eukaryotes. P falciparum GRASPs (PFGRASPs) are also notable in that each analogue possesses a different membrane anchoring mechanism, with PFGRASP1 possessing a myristoylation motif similar to human GRASPs while PFGRASP2 possesses an amphipathic helix similar to yeast GRASPs. So far, there is no research capable of elucidating the reasons behind the presence of two significantly different analogues in P. falciparum or their exact role in the parasite’s metabolism. To that end, we intend on investigating these questions via the biophysical characterization and comparison of the PFGRASP isoforms by chromatographic, optic and calorimetric methods.