Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality

Charles Hillier, Mercedes Pardo, Lu Yu, Ellen Bushell, Theo Sanderson, Tom Metcalf, Colin Herd, Burcu Anar, Julian C. Rayner, Oliver Billker, Jyoti S. Choudhary
2019 Cell Reports  
Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing Plasmodium parasites being uncharacterized. We report a large-scale protein interaction network in Plasmodium schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species,
more » ... entifies >20,000 putative protein interactions, organized into 600 protein clusters. We validate selected interactions, assigning functions in chromatin regulation to previously unannotated proteins and suggesting a role for an EELM2 domain-containing protein and a putative microrchidia protein as mechanistic links between AP2-domain transcription factors and epigenetic regulation. Our interactome represents a high-confidence map of the native organization of core cellular processes in Plasmodium parasites. The network reveals putative functions for uncharacterized proteins, provides mechanistic and structural insight, and uncovers potential alternative therapeutic targets.
doi:10.1016/j.celrep.2019.07.019 pmid:31390575 pmcid:PMC6693557 fatcat:pncp4i3e55bpdniknungxj7fo4