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Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry

Abstract

The annotated genomes of organisms define a ‘blueprint’ of their possible gene products. Post-genome analyses attempt to confirm and modify the annotation and impose a sense of the spatial, temporal and developmental usage of genetic information by the organism. Here we describe a large-scale, high-accuracy (average deviation less than 0.02 Da at 1,000 Da) mass spectrometric proteome analysis1,2,3 of selected stages of the human malaria parasite Plasmodium falciparum. The analysis revealed 1,289 proteins of which 714 proteins were identified in asexual blood stages, 931 in gametocytes 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 contain 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.

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Figure 1: Differential extraction of parasite-infected red blood cells (RBCs) and flow chart of MS analysis.
Figure 2: Schematic representation of proteomic data.
Figure 3: LCCL/lectin domain proteins expressed in sexual stages of P. falciparum.
Figure 4: Refinement of gene structure and re-annotation using proteomic data.

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Acknowledgements

We thank our colleagues for help and discussions. This work was supported by the Danish National Research Foundation, the Dutch Science Foundation (NWO), the European Union and the World Health Organization (WHO) Special Program for Research and Training in Tropical Diseases.

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Correspondence to Hendrik G. Stunnenberg or Matthias Mann.

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The authors declare that they have no competing financial interests.

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Sequence data for the genes newly annotated according to the present study can be found at http://www.sanger.ac.uk/Projects/P_falciparum.

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Lasonder, E., Ishihama, Y., Andersen, J. et al. Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature 419, 537–542 (2002). https://doi.org/10.1038/nature01111

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