A plasma membrane Ca(2+)-ATPase (PMCA) from the liver fluke, Fasciola hepatica

Moore, Catherine M., Hoey, Elizabeth M., Trudgett, Alan and Timson, David J. 2012. A plasma membrane Ca(2+)-ATPase (PMCA) from the liver fluke, Fasciola hepatica. International Journal for Parasitology. 42 (9), pp. 851-858. https://doi.org/10.1016/j.ijpara.2012.06.003

TitleA plasma membrane Ca(2+)-ATPase (PMCA) from the liver fluke, Fasciola hepatica
TypeJournal article
AuthorsMoore, Catherine M., Hoey, Elizabeth M., Trudgett, Alan and Timson, David J.
Abstract

Fasciolosis is a parasitic infection by the liver fluke Fasciola hepatica, which costs the global agricultural community over US $2 billion per year. Its prevalence is rising due to factors such as climate change and drug resistance. ATP-dependent membrane transporters are considered good potential drug targets as they are essential for cellular processes and are in an exposed, accessible position in the cell. Immunolocalisation studies demonstrated that a plasma membrane calcium ATPase (PMCA) was localised to the parenchymal tissue in F. hepatica. The coding sequence for a F. hepatica PMCA (FhPMCA) has been obtained. This sequence encodes a 1,163 amino acid protein which contains motifs which are commonly conserved in PMCAs. Molecular modelling predicted that the protein has 10 transmembrane segments which include a potential calcium ion binding site and phosphorylation motif. FhPMCA interacts with the calmodulin-like protein FhCaM1, but not the related proteins FhCaM2 or FhCaM3, in a calcium-ion dependent manner. This interaction occurs through a region in the C-terminal region of FhPMCA which most likely adopts an α-helical conformation. When FhPMCA was heterologously expressed in a budding yeast strain deleted for its PMCA (Pmc1p), it restored viability. Microsomes prepared from these yeast cells had calcium ion stimulated ATPase activity which was inhibited by the known PMCA inhibitors, bisphenol and eosin. The potential of FhPMCA as a new drug target is discussed.

JournalInternational Journal for Parasitology
Journal citation42 (9), pp. 851-858
ISSN0020-7519
Year2012
PublisherElsevier
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ijpara.2012.06.003
Web address (URL)https://doi.org/10.1016/j.ijpara.2012.06.003
Publication dates
PublishedAug 2012

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