Review

Heterologous expression of plasmodial proteins for structural studies and functional annotation

Lyn-Marie Birkholtz¹ , Gregory Blatch² , Theresa L Coetzer³ , Heinrich C Hoppe^1,4 , Esmaré Human¹ , Elizabeth J Morris^1,5 , Zoleka Ngcete¹ , Lyndon Oldfield⁴ , Robyn Roth⁴ , Addmore Shonhai⁶ , Linda Stephens² and Abraham I Louw¹

¹  Department of Biochemistry, University of Pretoria, Pretoria, South Africa

²  Department of Biochemistry, Microbiology & Biotechnology, Rhodes University, Grahamstown, South Africa

³  Department of Molecular Medicine and Haematology, University of the Witwatersrand/National Health Laboratory Service (NHLS), Johannesburg, South Africa

⁴  Council for Scientific and Industrial Research, CSIR Biosciences, Pretoria, South Africa

⁵  African Centre for Gene Technologies (Joint initiative of the CSIR, the University of Pretoria and the University of the Witwatersrand), Pretoria, South Africa

⁶  Department of Biochemistry and Microbiology, Zululand University, Kwadlangezwa, South Africa

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Malaria Journal 2008, 7:197doi:10.1186/1475-2875-7-197

Published:	1 October 2008

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 cost-effective 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.