title: Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Oehring
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Woodcroft
authors.forename: Suzette
authors.initials: S
authors.lastname: Moes
authors.forename: Johanna
authors.initials: J
authors.lastname: Wetzel
authors.forename: Olivier
authors.initials: O
authors.lastname: Dietz
authors.forename: Andreas
authors.initials: A
authors.lastname: Pulfer
authors.forename: Chaitali
authors.initials: C
authors.lastname: Dekiwadia
authors.forename: Pascal
authors.initials: P
authors.lastname: Maeser
authors.forename: Christian
authors.initials: C
authors.lastname: Flueck
authors.forename: Kathrin
authors.initials: K
authors.lastname: Witmer
authors.forename: Nicolas M B
authors.initials: NM
authors.lastname: Brancucci
authors.forename: Igor
authors.initials: I
authors.lastname: Niederwieser
authors.forename: Paul
authors.initials: P
authors.lastname: Jenoe
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.forename: Till S
authors.initials: TS
authors.lastname: Voss
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009687:Nuclear Proteins / Q000302:isolation & purification* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D015800:Protozoan Proteins