An aspartyl protease directs malaria effector proteins to the host cell

被引：245

作者：

Boddey, Justin A. ^{[1
]}

Hodder, Anthony N. ^{[1
]}

Guenther, Svenja ^{[1
]}

Gilson, Paul R. ^{[2
]}

Patsiouras, Heather ^{[3
]}

Kapp, Eugene A. ^{[3
]}

Pearce, J. Andrew ^{[1
]}

de Koning-Ward, Tania F. ^{[4
]}

Simpson, Richard J. ^{[1
,3
]}

Crabb, Brendan S. ^{[2
]}

Cowman, Alan F. ^{[1
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia

[2] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia

[3] Ludwig Inst Canc Res, Joint Prote Facil, Melbourne, Vic 3050, Australia

[4] Deakin Univ, Waurn Ponds 3217, Australia

来源：

NATURE | 2010年 / 463卷 / 7281期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM EXPORT ELEMENT; ENDOPLASMIC-RETICULUM; PARASITE PROTEINS; HIV-1; PROTEASE; TRAFFICKING; EXPRESSION; VIRULENCE; CYTOADHERENCE; INVASION;

D O I：

10.1038/nature08728

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：627 / U52

页数：7

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