Back to Search
Start Over
An aspartyl protease directs malaria effector proteins to the host cell.
- Source :
-
Nature [Nature] 2010 Feb 04; Vol. 463 (7281), pp. 627-31. - Publication Year :
- 2010
-
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 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.
- Subjects :
- Amino Acid Motifs
Animals
Antimalarials pharmacology
Aspartic Acid Endopeptidases genetics
Aspartic Acid Endopeptidases isolation & purification
Endoplasmic Reticulum enzymology
Endoplasmic Reticulum metabolism
Erythrocytes cytology
Erythrocytes parasitology
HIV Protease Inhibitors pharmacology
Humans
Malaria, Falciparum metabolism
Malaria, Falciparum pathology
Plasmodium falciparum enzymology
Plasmodium falciparum genetics
Protein Processing, Post-Translational drug effects
Protein Transport
Protozoan Proteins chemistry
Aspartic Acid Endopeptidases metabolism
Erythrocytes metabolism
Malaria, Falciparum blood
Malaria, Falciparum parasitology
Plasmodium falciparum metabolism
Protein Sorting Signals
Protozoan Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 463
- Issue :
- 7281
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 20130643
- Full Text :
- https://doi.org/10.1038/nature08728