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An aspartyl protease directs malaria effector proteins to the host cell
journal contribution
posted on 2010-02-04, 00:00 authored by J Boddey, A Hodder, S Gunther, P Gilson, H Patsiouras, E Kapp, A Pearce, Tania De Koning-WardTania De Koning-Ward, R Simpson, B Crabb, A CowmanPlasmodium 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 mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.
History
Journal
NatureVolume
463Issue
7281Pagination
627 - 631Publisher
Nature Publishing GroupLocation
London, EnglandPublisher DOI
ISSN
0028-0836eISSN
1476-4687Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2010, Nature Publishing GroupUsage metrics
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