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Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis
- Source :
- Biochemical and Biophysical Research Communications. 450:1427-1432
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of Plasmodium falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.
- Subjects :
- Signal peptide
Molecular Sequence Data
Plasmodium falciparum
Biophysics
Biology
Biochemistry
Plasmodium
Article
Heat shock protein
parasitic diseases
Animals
Aspartic Acid Endopeptidases
Amino Acid Sequence
Molecular Biology
Peptide sequence
Heat-Shock Proteins
Signal peptidase
Endoplasmic reticulum
Cell Biology
biology.organism_classification
Cell biology
Germ Cells
Microscopy, Fluorescence
Proteolysis
Signal peptide peptidase
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 450
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....d0805bc8738c509a2d1bf4beb8b74c91