Heterologous expression of plasmodial proteins for structural studies and functional annotation

Abstract

Malaria remains the world's most devastating tropical infectious disease with as many as 40% of the world population living in risk areas. The widespread resistance of Plasmodium parasites to the costeffective chloroquine and antifolates has forced the introduction of more costly drug combinations, such as Coartem ® . In the absence of a vaccine in the foreseeable future, one strategy to address the growing malaria problem is to identify and characterize new and durable antimalarial drug targets, the majority of which are parasite proteins. Biochemical and structure-activity analysis of these proteins is ultimately essential in the characterization of such targets but requires large amounts of functional protein. Even though heterologous protein production has now become a relatively routine endeavour for most proteins of diverse origins, the functional expression of soluble plasmodial proteins is highly problematic and slows the progress of antimalarial drug target discovery. Here the status quo of heterologous production of plasmodial proteins is presented, constraints are highlighted and alternative strategies and hosts for functional expression and annotation of plasmodial proteins are reviewed.

RH5–Basigin interaction plays a major role in the host tropism of Plasmodium falciparum

“…In principle, the species specificity of known host-parasite interactions could be examined using recombinant proteins, but the technical challenges associated with expressing functional Plasmodium proteins in a recombinant form have made this approach difficult thus far (11). There also are multiple points in the complex Plasmodium life cycle that could represent restriction points, and some evidence suggests that transmission of Laverania to anthropophilic Anopheles species, for example, may be restricted (12).…”

Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking Antibodies

“…Progress towards a field-deployable TBV has been hampered by challenges in expressing full-length, high-quality recombinant P. falciparum protein libraries in sufficient quantities for functional screening [38,39]. High-throughput protein expression platforms have been notoriously difficult to establish; the Plasmodium genome is A/T rich (over 80%) with abundant repeat regions [16].…”

Identify Secretory Protein of Malaria Parasite with Modified Quadratic Discriminant Algorithm and Amino Acid Composition

“…Thus the developing effective drugs and vaccines against this parasite are urgent. Parasite secretes an array of proteins within the host erythrocyte and beyond to facilitate its own survival within the host cell and for immunomodulation [2]. These proteins secreted by parasite can serve as potential drug or vaccine targets.…”