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Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum

Sophie C Oehring12, Ben J Woodcroft3, Suzette Moes4, Johanna Wetzel12, Olivier Dietz12, Andreas Pulfer12, Chaitali Dekiwadia3, Pascal Maeser12, Christian Flueck12, Kathrin Witmer12, Nicolas MB Brancucci12, Igor Niederwieser12, Paul Jenoe4, Stuart A Ralph3 and Till S Voss12*

Author Affiliations

1 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland

2 University of Basel, Petersplatz 1, Basel 4003, Switzerland

3 Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, 30 Flemington Road, Parkville 3010, Australia

4 Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland

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Genome Biology 2012, 13:R108  doi:10.1186/gb-2012-13-11-r108

Published: 26 November 2012

Abstract

Background

The post-genomic era of malaria research provided unprecedented insights into the biology of Plasmodium parasites. Due to the large evolutionary distance to model eukaryotes, however, we lack a profound understanding of many processes in Plasmodium biology. One example is the cell nucleus, which controls the parasite genome in a development- and cell cycle-specific manner through mostly unknown mechanisms. To study this important organelle in detail, we conducted an integrative analysis of the P. falciparum nuclear proteome.

Results

We combined high accuracy mass spectrometry and bioinformatic approaches to present for the first time an experimentally determined core nuclear proteome for P. falciparum. Besides a large number of factors implicated in known nuclear processes, one-third of all detected proteins carry no functional annotation, including many phylum- or genus-specific factors. Importantly, extensive experimental validation using 30 transgenic cell lines confirmed the high specificity of this inventory, and revealed distinct nuclear localization patterns of hitherto uncharacterized proteins. Further, our detailed analysis identified novel protein domains potentially implicated in gene transcription pathways, and sheds important new light on nuclear compartments and processes including regulatory complexes, the nucleolus, nuclear pores, and nuclear import pathways.

Conclusion

Our study provides comprehensive new insight into the biology of the Plasmodium nucleus and will serve as an important platform for dissecting general and parasite-specific nuclear processes in malaria parasites. Moreover, as the first nuclear proteome characterized in any protist organism, it will provide an important resource for studying evolutionary aspects of nuclear biology.

Keywords:
Malaria; Plasmodium falciparum; Nucleus; Proteomics; Bioinformatics; IFA; Transcription; Nucleolus; Nuclear pore; Transfection