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Endocytobiosis Cell Res. 17, 1 (2006)
Analysis of the Plasmodium falciparum proteome by high accuracy mass spectrometry
Edwin Lasonder*,$, Yasushi Ishihama*, Jens S. Andersen*, Adriaan Vermunt$, Arnab
Pain¥, Robert W. Sauerwein§, Wijnand Eling§, Neil Hall¥, Andrew P. Waters#, Hendrik
G. Stunnenberg$, Matthias Mann*
*Center
for Experimental BioInformatics(CEBI), Department of Biochemistry and Molecular Biology, Universi-
tyof Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark; $Department of Molecular Biology,
NCMLS, University of Nijmegen, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherland; §Department of
Medical Microbiology, NCMLS, University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; ¥Welcome Trust Sanger Institute, WelcomeTrust Sanger Institute Genome Campus, Hinxton, Cambridge DB101SA, UK; #Leiden Malaria Research Group, Department of Parasitology, Centre for Infectious
Disease, Leiden University Medical Center, LUMC, Albinusdreef 2, 2333 ZA Leiden
Recent developments in highly sensitive mass-spectrometric techniques combined with
database homology searches have revolutionized protein analysis and identification. Determination of the ‘proteome’ – the complement of proteins expressed in a given stage - is
instrumental in identification of disease markers, elucidate biological pathways and validate drug-targets. Parasites, organelles or protein complexes can be analysed by massspectrometric measurements to identify stage-specific, secreted and membraneassociated proteins.
In collaboration with the laboratory of Matthias Mann, Odense University Denmark, we
have used large-scale high accuracy mass spectrometric proteome analysis of asexual
and sexual blood stages selected stages of the human malaria parasite Plasmodium falciparum to identify proteins involved in sexual stage biology. The analysis revealed 1,289
proteins of which 714 proteins were identified in asexual blood stages (left panel), 931 in
gametocytes (right panel) and 645 in gametes. The last two groups provide insights into
the biology of the sexual stages of the parasite, and include conserved, stage-specific, secreted and membrane-associated proteins. A subset of these proteins contains domains
that indicate a role in cell–cell interactions, and therefore can be evaluated as potential
components of a malaria vaccine formulation. We also report a set of peptides with significant matches in the parasite genome but not in the protein set predicted by computational
methods. Post genome analyses have been used to confirm and modify the annotation
and impose a sense of the spatial, temporal and developmental utilisation of genetic information by the organism.
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