Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.
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Date
2019-08-06Author
Hillier, C
Pardo, M
Yu, L
Bushell, E
Sanderson, T
Metcalf, T
Herd, C
Anar, B
Rayner, JC
Billker, O
Choudhary, JS
Type
Journal Article
Metadata
Show full item recordAbstract
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, identifies >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.
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Subject
Animals
Mice
Rats
Plasmodium
Plasmodium falciparum
Protozoan Proteins
Electrophoresis, Polyacrylamide Gel
Species Specificity
Female
Tandem Mass Spectrometry
Protein Interaction Maps
Research team
Functional Proteomics Group
Language
eng
Date accepted
2019-07-08
License start date
2019-08
Citation
Cell reports, 2019, 28 (6), pp. 1635 - 1647.e5
Publisher
CELL PRESS