An essential signal peptide peptidase identified in an RNAi screen of serine peptidases of trypanosoma brucei
| العنوان: | An essential signal peptide peptidase identified in an RNAi screen of serine peptidases of trypanosoma brucei |
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| المؤلفون: | Alana Hamilton, Elaine Brown, Pieter Van der Veken, Jeremy C. Mottram, Koen Augustyns, Catherine X. Moss |
| المصدر: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0123241 (2015) |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Proteases, Serine Proteinase Inhibitors, Trypanosoma brucei brucei, Protozoan Proteins, Oligopeptidase, lcsh:Medicine, Trypanosoma brucei, Cell Line, Serine, Mice, RNA interference, Animals, Aspartic Acid Endopeptidases, education, lcsh:Science, education.field_of_study, Multidisciplinary, biology, Serine Endopeptidases, lcsh:R, Gene targeting, biology.organism_classification, Dipeptidyl peptidase 8, 3. Good health, Biochemistry, RNA Interference, lcsh:Q, Signal peptide peptidase, Engineering sciences. Technology, Research Article |
| الوصف: | The serine peptidases of Trypanosoma brucei have been viewed as potential drug targets. In particular, the S9 prolyl oligopeptidase subfamily is thought to be a good avenue for drug discovery. This is based on the finding that some S9 peptidases are secreted and active in the mammalian bloodstream, and that they are a class of enzyme against which drugs have successfully been developed. We collated a list of all serine peptidases in T. brucei, identifying 20 serine peptidase genes, of which nine are S9 peptidases. We screened all 20 serine peptidases by RNAi to determine which, if any, are essential for bloodstream form T. brucei survival. All S9 serine peptidases were dispensable for parasite survival in vitro, even when pairs of similar genes, coding for oligopeptidase B or prolyl oligopeptidase, were targeted simultaneously. We also found no effect on parasite survival in an animal host when the S9 peptidases oligopeptidase B, prolyl oligopeptidase or dipeptidyl peptidase 8 were targeted. The only serine peptidase to emerge from the RNAi screen as essential was a putative type-I signal peptide peptidase (SPP1). This gene was essential for parasite survival both in vitro and in vivo. The growth defect conferred by RNAi depletion of SPP1 was rescued by expression of a functional peptidase from an RNAi resistant SPP1 gene. However, expression of catalytically inactive SPP1 was unable to rescue cells from the SPP1 depleted phenotype, demonstrating that SPP1 serine peptidase activity is necessary for T. brucei survival. |
| وصف الملف: | pdf; application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cdb2ebce5f6e378457f6ef9c6d2cb664 https://hdl.handle.net/10067/1255430151162165141 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cdb2ebce5f6e378457f6ef9c6d2cb664 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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