| 1 |
IPD2610 |
Divergent Plasmodium Aurora related kinases ARK1 and ARK2 coordinate spindle biogenesis and karyokinesis by regulating key centromere-kinetochore proteins |
Dr. T S Keshava Prasad |
Human malaria parasite Plasmodium falciparum is a unicellular eukaryote that proliferates within human and mosquito hosts via highly specialized cell division processes that are markedly different from those of conventional eukaryotic model organisms. Aurora kinases are central regulators of eukaryotic cell division. Although Plasmodium species encode three divergent Aurora-related kinases...
Human malaria parasite Plasmodium falciparum is a unicellular eukaryote that proliferates within human and mosquito hosts via highly specialized cell division processes that are markedly different from those of conventional eukaryotic model organisms. Aurora kinases are central regulators of eukaryotic cell division. Although Plasmodium species encode three divergent Aurora-related kinases (ARK1–3) that are essential for parasite survival. In this study, we show that conditional knockout of PfARK2 disrupts spindle formation, leading to defects in karyokinesis and subsequent failure of cytokinesis. Recently, we reported similar role for PfARK1; however, the underlying mechanisms remained unclear. Phosphoproteomic analyses reveal that PfARK1 and PfARK2 target distinct sets of substrates, several of which are key kinetochore proteins. Strikingly, PfARK2 regulates the phosphorylation-dependent localization of PfCENH3, a centromere-specific histone H3 variant essential for spindle assembly and nuclear division. NUF2, an outer kinetochore component, is differentially regulated by both kinases at distinct sites. The regulation of these proteins by PfARK1/2 is critical for proper kinetochore assembly and spindle formation. Furthermore, we have identified small-molecule inhibitors targeting these Aurora kinases that effectively block asexual stage proliferation of P. falciparum by disrupting PfARK1/2-dependent processes. These findings provide novel insights into parasite division and highlight a promising avenue for the development of novel antimalarial therapies.
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NITTE, Deemed to be University, Mangaluru, Karnataka, India |
Bottom-up |
2027-06-04 |
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| 2 |
IPD1816 |
Mycobacterium tuberculosis PknB phosphoproteome profiling |
Dr. T S Keshava Prasad |
Mass spectrometry-based proteomic characterization of Mycobacterium tuberculosis protein kinase B (PknB), including PknB-associated protein interactors and phosphorylation-dependent changes associated with PknB juxtamembrane (JM) mutants. The interactome experiment compared wild-type PknB (Rv-pptr-B::pknB), a PknB-JMMim mutant, and a PknB-JMAbl mutant using FLAG-based immunoprecipitation followed by LC-MS/MS. The phosphoproteomic experiment profiled wild-type PknB,...
Mass spectrometry-based proteomic characterization of Mycobacterium tuberculosis protein kinase B (PknB), including PknB-associated protein interactors and phosphorylation-dependent changes associated with PknB juxtamembrane (JM) mutants. The interactome experiment compared wild-type PknB (Rv-pptr-B::pknB), a PknB-JMMim mutant, and a PknB-JMAbl mutant using FLAG-based immunoprecipitation followed by LC-MS/MS. The phosphoproteomic experiment profiled wild-type PknB, PknB-JMMim, and PknB-JMAbl using phosphopeptide enrichment followed by DIA LC-MS/MS on an Orbitrap Astral Zoom. The resulting datasets were used to identify PknB-associated proteins and quantify phosphorylation-site changes.
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NITTE, Deemed to be University, Mangaluru, Karnataka, India |
Bottom-up |
2027-09-28 |
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