An aspartyl protease directs malaria effector proteins to the host cell

作者：Boddey Justin A; Hodder Anthony N; Guenther Svenja; Gilson Paul R; Patsiouras Heather; Kapp Eugene A; Pearce J Andrew; de Koning Ward Tania F; Simpson Richard J; Crabb Brendan S; Cowman Alan F^*

来源：Nature, 2010, 463(7281): 627-U52.

DOI：10.1038/nature08728

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.

• 出版日期2010-2-4
• 单位河北医科大学