A protein interaction network of the malaria parasite Plasmodium falciparum.
Plasmodium falciparum causes the most severe form of malaria and kills up to 2.7 million people annually. Despite the global importance of P. falciparum, the vast majority of its proteins have not been characterized experimentally. Here we identify P. falciparum protein-protein interactions using a high-throughput version of the yeast two-hybrid assay that circumvents the difficulties in expressing P. falciparum proteins in Saccharomyces cerevisiae. From more than 32,000 yeast two-hybrid screens with P. falciparum protein fragments, we identified 2,846 unique interactions, most of which include at least one previously uncharacterized protein. Informatic analyses of network connectivity, coexpression of the genes encoding interacting fragments, and enrichment of specific protein domains or Gene Ontology annotations were used to identify groups of interacting proteins, including one implicated in chromatin modification, transcription, messenger RNA stability and ubiquitination, and another implicated in the invasion of host cells. These data constitute the first extensive description of the protein interaction network for this important human pathogen.
LaCount
Douglas J
DJ
Howard Hughes Medical Institute, University of Washington, Box 357730, Seattle, Washington 98195, USA.
Vignali
Marissa
M
Chettier
Rakesh
R
Phansalkar
Amit
A
Bell
Russell
R
Hesselberth
Jay R
JR
Schoenfeld
Lori W
LW
Ota
Irene
I
Sahasrabudhe
Sudhir
S
Kurschner
Cornelia
C
Fields
Stanley
S
Hughes
Robert E
RE
D000818:Animals; D016778:Malaria, Falciparum / Q000469:parasitology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D020798:Two-Hybrid System Techniques; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D010446:Peptide Fragments; D015800:Protozoan Proteins; D037521:Virulence Factors