Casein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate the function of the PfCK2α catalytic subunit in gametocytes, the sexual forms of the parasite that are essential for malaria transmission. We show that PfCK2α localizes to the nucleus and cytoplasm in asexual and sexual parasites alike. Conditional knockdown of PfCK2α expression prevented the transition of stage IV into transmission-competent stage V gametocytes, whereas the conditional knockout of pfck2a completely blocked gametocyte maturation already at an earlier stage of sexual differentiation. In summary, our results demonstrate that PfCK2α is not only essential for asexual but also sexual development of P. falciparum blood-stage parasites and encourage studies exploring PfCK2α as a potential target for dual-active antimalarial drugs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954856 | PMC |
| http://dx.doi.org/10.1038/s42003-021-01873-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent advances in microwave-assisted synthesis of triazoles and their derivatives: a green approach toward sustainable development methods.
RSC Adv
January 2025
Department of Chemistry, Manipal University Jaipur VPO-Dehmi-Kalan, Off Jaipur Ajmer Express Way Jaipur Rajasthan 303007 India
Triazole, a nitrogen-containing five-membered heterocycle with two isomeric forms, 1,2,3-triazole and 1,2,4-triazole, has proven to be a valuable component in the pharmaceutical domain. Owing to its widespread utility in drug development, pharmaceutical and medicinal chemistry, several synthetic methods have been explored, such as different catalytic systems, solvents, and heating methodologies in recent years. However, some methods were associated with several limitations, such as harsh reaction conditions, high temperatures, low atom economy, and long reaction times.
View Article and Find Full Text PDFγ-secretase facilitates retromer-mediated retrograde transport.
J Cell Sci
January 2025
Department of Genetics, Yale School of Medicine, USA.
Retromer mediates retrograde transport of protein cargos from endosomes to the trans-Golgi network (TGN). γ-secretase is a protease that cleaves the transmembrane domain of its target proteins. Although retromer can form a stable complex with γ-secretase, the functional consequences of this interaction are not known.
View Article and Find Full Text PDFCoumarin Analogues as Promising Anti-Obesity Agents: In Silico Design, Synthesis, and In Vitro Pancreatic Lipase Inhibitory Activity.
Chem Biol Drug Des
January 2025
Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani, Rajasthan, India.
A set of coumarin-3-carboxamide analogues were designed, synthesized, and evaluated for their ability to impede pancreatic lipase (PL) activity. Out of all the analogues, 5dh and 5de demonstrated promising inhibitory activity against PL, as indicated by their respective IC values of 9.20 and 11.
View Article and Find Full Text PDFInsights into the flexibility of the domain-linking loop in actinobacterial coproheme decarboxylase through structures and molecular dynamics simulations.
Protein Sci
February 2025
Department of Chemistry, Institute of Biochemistry, BOKU University, Vienna, Austria.
Prokaryotic heme biosynthesis in Gram-positive bacteria follows the coproporphyrin-dependent heme biosynthesis pathway. The last step in this pathway is catalyzed by the enzyme coproheme decarboxylase, which oxidatively transforms two propionate groups into vinyl groups yielding heme b. The catalytic reaction cycle of coproheme decarboxylases exhibits four different states: the apo-form, the substrate (coproheme)-bound form, a transient three-propionate intermediate form (monovinyl, monopropionate deuteroheme; MMD), and the product (heme b)-bound form.
View Article and Find Full Text PDFCryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.
Protein Sci
February 2025
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!