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

Animals Electrophoresis, Polyacrylamide Gel Female Mice Plasmodium / genetics Plasmodium falciparum / genetics Protein Interaction Maps Protozoan Proteins / metabolism Rats Species Specificity Tandem Mass Spectrometry
Plasmodium Plasmodium berghei Plasmodium falciparum Plasmodium knowlesi blue native-PAGE interaction network interactome malaria protein-protein interactions

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
06 08 2019
Historique:
received: 13 12 2018
revised: 28 05 2019
accepted: 08 07 2019
entrez: 8 8 2019
pubmed: 8 8 2019
medline: 1 9 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2019.07.019 PMID: 31390575 PMC: PMC6693557
pubmed: 31390575
pii: S2211-1247(19)30909-X
doi: 10.1016/j.celrep.2019.07.019
pmc: PMC6693557
pii:
doi:

Substances chimiques

Protozoan Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1635-1647.e5

Subventions

Organisme : Wellcome Trust
ID : 206194/Z/17/Z
Pays : United Kingdom

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Charles Hillier (C)

Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.

Mercedes Pardo (M)

Functional Proteomics, The Institute of Cancer Research, London SW7 3RP, UK. Electronic address: mercedes.pardocalvo@icr.ac.uk.

Lu Yu (L)

Functional Proteomics, The Institute of Cancer Research, London SW7 3RP, UK.

Ellen Bushell (E)

Department of Molecular Biology, The Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, Sweden.

Theo Sanderson (T)

Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.

Tom Metcalf (T)

Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.

Colin Herd (C)

Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.

Burcu Anar (B)

Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.

Julian C Rayner (JC)

Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.

Oliver Billker (O)

Department of Molecular Biology, The Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, Sweden. Electronic address: oliver.billker@umu.se.

Jyoti S Choudhary (JS)

Functional Proteomics, The Institute of Cancer Research, London SW7 3RP, UK. Electronic address: jyoti.choudhary@icr.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Techniques d'investigation › Techniques électrochimiques › Électrophorèse › Électrophorèse sur gel de polyacrylamide › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Eucaryotes › Alveolata › Apicomplexa › Haemosporida › Plasmodium › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Eucaryotes › Alveolata › Apicomplexa › Haemosporida › Plasmodium › Plasmodium falciparum › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Cartes d'interactions protéiques › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de protozoaire › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Phénomènes biologiques › Spécificité d'espèce › Landscape of the Plasmodium Interactome...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse en tandem › Landscape of the Plasmodium Interactome...