Journal article
An aspartyl protease directs malaria effector proteins to the host cell
JA Boddey, AN Hodder, S Günther, PR Gilson, H Patsiouras, EA Kapp, JA Pearce, TF De Koning-Ward, RJ Simpson, BS Crabb, AF Cowman
Nature | NATURE PUBLISHING GROUP | Published : 2010
DOI: 10.1038/nature08728
Abstract
Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical matu..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank the Australian Red Cross Blood Bank for the provision of human blood and serum, the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH for providing HIV protease inhibitors and MR4 (ATCC) for plasmepsin V antibodies, contributed by D. Goldberg. This work was supported by the National Health and Medical Research Council, and a grant from the National Institutes of Health (RO1 AI44008). J.A.B. is an NHMRC Peter Doherty postdoctoral Fellow and A. F. C. is an International Research Scholar of the Howard Hughes Medical Institute and an Australia Fellow.