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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Pandey, A. & Mann, M. Proteomics to study genes and genomes. Nature 405, 837–846 (2000)
Link, A. J. et al. Direct analysis of protein complexes using mass spectrometry. Nature Biotechnol. 17, 676–682 (1999)
Griffin, T. J. & Aebersold, R. Advances in proteome analysis by mass spectrometry. J. Biol. Chem. 276, 45497–45500 (2001)
Bruce, M. C., Alano, P., Duthie, S. & Carter, R. Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development. Parasitology 100, 191–200 (1990)
Richie, T. L. & Saul, A. Progress and challenges for malaria vaccines. Nature 415, 694–701 (2002)
Kocken, C. H. et al. Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum. Mol. Biochem. Parasitol. 61, 59–68 (1993)
Perkins, D. N., Pappin, D. J., Creasy, D. M. & Cottrell, J. S. Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551–3567 (1999)
Gardner, M. J. et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511 (2002)
van Dijk, M. R. et al. A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153–164 (2001)
Alano, P. et al. COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies. Mol. Biochem. Parasitol. 74, 143–156 (1995)
Wickham, M. E. et al. Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes. EMBO J. 20, 5636–5649 (2001)
Cowman, A. F. et al. Functional analysis of proteins involved in Plasmodium falciparum merozoite invasion of red blood cells. FEBS Lett. 476, 84–88 (2000)
Rahlfs, S., Fischer, M. & Becker, K. Plasmodium falciparum possesses a classical glutaredoxin and a second, glutaredoxin-like protein with a PICOT homology domain. J. Biol. Chem. 276, 37133–37140 (2001)
Fowler, R. E. et al. Microtubule associated motor proteins of Plasmodium falciparum merozoites. Mol. Biochem. Parasitol. 117, 187–200 (2001)
Templeton, T. J., Keister, D. B., Muratova, O., Procter, J. L. & Kaslow, D. C. Adherence of erythrocytes during exflagellation of Plasmodium falciparum microgametes is dependent on erythrocyte surface sialic acid and glycophorins. J. Exp. Med. 187, 1599–1609 (1998)
Delrieu, I. et al. PSLAP, a protein with multiple adhesive motifs, is expressed in Plasmodium falciparum gametocytes. Mol. Biochem. Parasitol. 121, 11–20 (2002)
Kuster, B., Mortensen, P., Andersen, J. S. & Mann, M. Mass spectrometry allows direct identification of proteins in large genomes. Proteomics 1, 641–650 (2001)
Rutherford, K. et al. Artemis: sequence visualization and annotation. Bioinformatics 16, 944–945 (2000)
Brooks, S. R. & Williamson, K. C. Proteolysis of Plasmodium falciparum surface antigen, Pfs230, during gametogenesis. Mol. Biochem. Parasitol. 106, 77–82 (2000)
Shevchenko, A., Wilm, M., Vorm, O. & Mann, M. Mass spectrometric sequencing of proteins from silver stained polyacrylamide gels. Anal. Chem. 68, 850–858 (1996)
Rappsilber, J., Ryder, U., Lamond, A. I. & Mann, M. Large-scale proteomic analysis of the human spliceosome. Genome Res. 12, 1231–1245 (2002)
Schultz, J., Milpetz, F., Bork, P. & Ponting, C. P. SMART, a simple modular architecture research tool: identification of signaling domains. Proc. Natl Acad. Sci. USA 95, 5857–5864 (1998)
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.
The authors declare that they have no competing financial interests.
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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