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Mol Cell Proteomics. 2018 Jan;17(1):111-120. doi: 10.1074/mcp.RA117.000088. Epub 2017 Oct 27.

A Global Survey of ATPase Activity in Plasmodium falciparum Asexual Blood Stages and Gametocytes.

Author information

1
From the ‡Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, Washington 98109.
2
§Department of Global Health, University of Washington, Seattle, Washington 98195.
3
¶Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352.
4
From the ‡Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, Washington 98109; christoph.grundner@cidresearch.org.

Abstract

Effective malaria control and elimination in hyperendemic areas of the world will require treatment of the Plasmodium falciparum (Pf) blood stage that causes disease as well as the gametocyte stage that is required for transmission from humans to the mosquito vector. Most currently used therapies do not kill gametocytes, a highly specialized, non-replicating sexual parasite stage. Further confounding next generation drug development against Pf is the unknown metabolic state of the gametocyte and the lack of known biochemical activity for most parasite gene products in general. Here, we take a systematic activity-based proteomics approach to survey the activity of the large and druggable ATPase family in replicating blood stage asexual parasites and transmissible, non-replicating sexual gametocytes. ATPase activity broadly changes during the transition from asexual schizonts to sexual gametocytes, indicating altered metabolism and regulatory roles of ATPases specific for each lifecycle stage. We further experimentally confirm existing annotation and predict ATPase function for 38 uncharacterized proteins. By mapping the activity of ATPases associated with gametocytogenesis, we assign biochemical activity to a large number of uncharacterized proteins and identify new candidate transmission blocking targets.

PMID:
29079720
PMCID:
PMC5750841
DOI:
10.1074/mcp.RA117.000088
[Indexed for MEDLINE]
Free PMC Article

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