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

Cell Reports
Charles HillierJyoti S Choudhary

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.

Citations

Aug 21, 2020·Molecular Systems Biology·Jessica M BryantArtur Scherf
Feb 23, 2020·International Journal of Molecular Sciences·Apichat Suratanee, Kitiporn Plaimas
Dec 4, 2019·Molecular & Cellular Proteomics : MCP·Daniela SalasLeonard J Foster
Oct 30, 2020·Molecular Microbiology·Leonardo AugustoWilliam J Sullivan
Jan 12, 2021·BioMed Research International·Kais GhediraHoucemeddine Othman
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Daniela SalasLeonard J Foster
May 29, 2021·Nature Communications·Eliana RealMara K N Lawniczak
May 21, 2021·Biochimica Et Biophysica Acta. Bioenergetics·Sergio Guerrero-CastilloSøren W Gersting
Jun 23, 2021·Nature Communications·Felix EversTaco W A Kooij
Aug 25, 2021·MBio·Julie M J VerhoefTaco W A Kooij
Aug 31, 2021·Trends in Parasitology·Dayana C Farhat, Mohamed-Ali Hakimi

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Datasets Mentioned

BETA
PXD010117

Methods Mentioned

BETA
two-hybrid
pull-down
gel filtration
electrophoresis
affinity purification
pull-downs
protein correlation
light microscopy
transfection
protein

Software Mentioned

PHYLIP
OrthoMCL
DOMINE
Mascot Science
pMT
randomForest R package
Protdist
REACTOME
MUSCLE
ContextMirror

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