An aspartyl protease directs malaria effector proteins to the host cell

Boddey, Justin A., Hodder, Anthony N., Gunther, Svenja, Gilson, Paul R., Patsiouras, Heather, Kapp, Eugene, Pearce, Andrew J., de Koning-Ward, Tania F., Simpson, Richard J., Crabb, Brendan S. and Cowman, Alan F. 2010, An aspartyl protease directs malaria effector proteins to the host cell, Nature, vol. 463, no. 7281, pp. 627-631, doi: 10.1038/nature08728.

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Title An aspartyl protease directs malaria effector proteins to the host cell
Author(s) Boddey, Justin A.
Hodder, Anthony N.
Gunther, Svenja
Gilson, Paul R.
Patsiouras, Heather
Kapp, Eugene
Pearce, Andrew J.
de Koning-Ward, Tania F.ORCID iD for de Koning-Ward, Tania F.
Simpson, Richard J.
Crabb, Brendan S.
Cowman, Alan F.
Journal name Nature
Volume number 463
Issue number 7281
Start page 627
End page 631
Total pages 5
Publisher Nature Publishing Group
Place of publication London, England
Publication date 2010-02-04
ISSN 0028-0836
Keyword(s) malaria
Summary 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 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.
Language eng
DOI 10.1038/nature08728
Field of Research 060108 Protein Trafficking
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2010, Nature Publishing Group
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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