A protein interaction network of the malaria parasite Plasmodium falciparum

Abstract

A powerful approach for understanding protein function is to identify which proteins bind to each other, as protein complexes are at the heart of most biological processes. Protein–protein interactions have now been mapped for one quarter of the malaria parasite's proteins. This large data set sheds new light on how parasites infect red blood cells and will be a vital tool for the development of new antimalarial drugs and vaccines. The primary data are freely available on the PlasmoDB database. Suthram et al. have used this new resource and find that the Plasmodium network has significantly less cross-species similarity than other eukaryotes. Its novel life style is reflected in a novel protein network, which therefore has a good chance of providing drug targets unique to the malaria parasite. Plasmodium falciparum causes the most severe form of malaria and kills up to 2.7 million people annually1. 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 annotations2 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.