Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.
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ICR Authors
Authors
Hillier, C
Pardo, M
Yu, L
Bushell, E
Sanderson, T
Metcalf, T
Herd, C
Anar, B
Rayner, JC
Billker, O
Choudhary, JS
Pardo, M
Yu, L
Bushell, E
Sanderson, T
Metcalf, T
Herd, C
Anar, B
Rayner, JC
Billker, O
Choudhary, JS
Document Type
Journal Article
Date
2019-08-06
Date Accepted
2019-07-08
Abstract
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.
Citation
Cell reports, 2019, 28 (6), pp. 1635 - 1647.e5
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Functional Proteomics Group