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Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
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2019 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 28, no 6, p. 1635-1647Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 28, no 6, p. 1635-1647
Keywords [en]
Plasmodium, blue native-PAGE, interactome, protein-protein interactions, interaction network, malaria, Plasmodium falciparum, Plasmodium berghei, Plasmodium knowlesi
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:umu:diva-162665DOI: 10.1016/j.celrep.2019.07.019ISI: 000478978200023PubMedID: 31390575OAI: oai:DiVA.org:umu-162665DiVA, id: diva2:1348524
Available from: 2019-09-04 Created: 2019-09-04 Last updated: 2019-09-04Bibliographically approved

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Bushell, EllenBillker, Oliver
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