Leishmania Donovani 90 kD Heat Shock Protein - Impact of Phosphosites on Parasite Fitness, Infectivity and Casein Kinase Affinity
| العنوان: | Leishmania Donovani 90 kD Heat Shock Protein - Impact of Phosphosites on Parasite Fitness, Infectivity and Casein Kinase Affinity |
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| المؤلفون: | Katharina Bartsch, Andrea MacDonald, Martin Wiese, Despina Smirlis, Heidi Rosenqvist, Joachim Clos, Antje Hombach-Barrigah, Damarys Loew, Gerald F. Späth, Florent Dingli, Najma Rachidi |
| المساهمون: | Rachidi, Najma, Blanc – Accords bilatéraux 2013 - Trans-signalisation: Un nouveau mécanisme permettant à Leishmania d'éviter la réponse immunitaire de la cellule hôte par la sécrétion de protéines de signalisation - - TranSig2013 - ANR-13-ISV3-0009 - Blanc – Accords bilatéraux 2013 - VALID, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP), Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Strathclyde [Glasgow], Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie [Paris], A.H.-B. and K.B. were supported by a grant from the Deutsche Forschungsgemeinschaft (CL120/8-1). Despina Smirlis and Najma Rachidi were supported by the ANR-13-ISV3-0009 grant. This work was supported by 'Région Ile-de-France' and FRM grants (D.L.)., ANR-13-ISV3-0009,TranSig,Trans-signalisation: Un nouveau mécanisme permettant à Leishmania d'éviter la réponse immunitaire de la cellule hôte par la sécrétion de protéines de signalisation(2013), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | Scientific Reports Scientific Reports, 2019, 9 (1), pp.5074. ⟨10.1038/s41598-019-41640-0⟩ Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.5074. ⟨10.1038/s41598-019-41640-0⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, [SDV]Life Sciences [q-bio], Molecular Sequence Data, lcsh:Medicine, Article, RS, 03 medical and health sciences, 0302 clinical medicine, Heat shock protein, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein phosphorylation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Amino Acid Sequence, HSP90 Heat-Shock Proteins, Phosphorylation, lcsh:Science, Infectivity, Multidisciplinary, biology, Chemistry, lcsh:R, Hsp90, 3. Good health, Cell biology, Complementation, [SDV] Life Sciences [q-bio], 030104 developmental biology, Microscopy, Fluorescence, Mutagenesis, Mutation, biology.protein, lcsh:Q, Casein kinase 1, Signal transduction, Casein Kinases, 030217 neurology & neurosurgery, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Leishmania donovani, Signal Transduction |
| الوصف: | Leishmania parasites are thought to control protein activity at the post-translational level, e.g. by protein phosphorylation. In the pathogenic amastigote, the mammalian stage of Leishmania parasites, heat shock proteins show increased phosphorylation, indicating a role in stage-specific signal transduction. Here we investigate the impact of phosphosites in the L. donovani heat shock protein 90. Using a chemical knock-down/genetic complementation approach, we mutated 11 confirmed or presumed phosphorylation sites and assessed the impact on overall fitness, morphology and in vitro infectivity. Most phosphosite mutations affected the growth and morphology of promastigotes in vitro, but with one exception, none of the phosphorylation site mutants had a selective impact on the in vitro infection of macrophages. Surprisingly, aspartate replacements mimicking the negative charge of phosphorylated serines or threonines had mostly negative impacts on viability and infectivity. HSP90 is a substrate for casein kinase 1.2-catalysed phosphorylation in vitro. While several putative phosphosite mutations abrogated casein kinase 1.2 activity on HSP90, only Ser289 could be identified as casein kinase target by mass spectrometry. In summary, our data show HSP90 as a downstream client of phosphorylation-mediated signalling in an organism that depends on post-transcriptional gene regulation. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84f6312d2191d6285c9b3caa2c5383ffTest https://hal-pasteur.archives-ouvertes.fr/pasteur-02874587/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....84f6312d2191d6285c9b3caa2c5383ff |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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