2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
March 6th, 2025
Version: 1
University of Cape Town
molecular biology
biorxiv

Heme Detoxification in the Malaria Parasite Plasmodium falciparum: A Time-Dependent Basal-Level Analysis

Garnie, L. F.Open in Google Scholar•Egan, T. J.Open in Google Scholar•Wicht, K. J.Open in Google Scholar

Malaria is a deadly disease for which therapeutic options are threatened by the rise of antimalarial resistance. Inhibiting the formation of hemozoin (the product of heme detoxification) in the digestive vacuole (DV) is the mechanism of action of numerous antimalarial drugs, including those in development as new therapies. This drug target remains attractive as hemozoin is an abiotic and non-mutable molecule, unique to the parasite. The underlying parasite biology of the heme detoxification pathway is complex and requires a deeper understanding. This study focuses on the DV of Plasmodium falciparum, utilizing confocal microscopy, immunoblotting and cellular fractionation techniques to study its native state over time. Using parameters such as the uptake into and growth of the DV, relative abundance of plasmepsins (PM) I and IV and basal levels of hemoglobin, heme and hemozoin, it was found that DV physiology in chloroquine (CQ)-sensitive NF54 parasites follows three distinct developmental phases: the lag-type growth (20 to 28 h), rapid growth phase (28 to 40 h) and the plateau (40 to 48 h). These phases hold specific characteristics with respect to the investigated parameters. In addition, key differences between CQ-sensitive NF54 and CQ-resistant Dd2 parasites were observed.

Similar Papers

biorxiv
Fri Mar 07 2025
Structural features of the amino acid sequences of Chromista nucleolin-like proteins
Nucleolins are multifunctional proteins localized in the centrosome and nucleus and involved in the processes of microtubule nucleation. Their structure is highly conserved in organisms that are evolutionarily distant from each other. The phylogeny of the kingdom Chromista was supported by marker genes, cell morphology and cytoskeletal features. In this study we identified general patterns of the ...
Petrova, D.
•
Potapova, N.
•
Bedoshvili, Y.
biorxiv
Fri Mar 07 2025
Novel DNA endonuclease activity of human ERK1 protein
ERK1 is a key kinase in the mitogen-activated protein kinase pathway, which transduces extracellular signals into cellular responses. Following triggering of the pathway, cytosolic ERK1 is phosphorylated and translocated into the nucleus to activate DNA-bound factors and target genes. This study reports a novel role of human ERK1 as a DNA endonuclease to catalyze single-strand DNA breaks without s...
Ju, S.
•
Jeong, J.
•
Joo, B. C.
•
Lee, S. J.
...•
Bunch, H.
biorxiv
Fri Mar 07 2025
A Robust Expression and Purification Protocol for the Production of the La Domain of Human LARP6
Human La-related protein 6 (HsLARP6) regulates the highly organized biosynthesis of type I procollagen polypeptides and affects proper assembly of procollagen peptides into heterotrimers of type I procollagen. HsLARP6-mediated regulation of collagen biosynthesis is mediated through interaction with the 5' stem loop (5'SL) motif found in type I and III collagen messenger RNA. Recent studies highlig...
Gordon, B. H.
•
Blackford, N.
•
Silvers, R.
biorxiv
Thu Mar 06 2025
Bacterial sirtuin CobB and PRPP synthase crosstalk in the regulation of protein acetylation in Escherichia coli
In bacteria, post-translational acetylation of lysine residues affects the activities of numerous proteins, thus constituting an important regulatory mechanism that influences bacterial growth and adaptation to various environments. Conversely, the modification level of some lysine residues is controlled by deacetylases that remove the acetyl group. Most bacterial deacetylases are homologous to eu...
Walter, B. M.
•
Morcinek-Orlowska, J.
•
Szulc, A.
•
Lovering, A. L.
...•
Glinkowska, M. K.
biorxiv
Thu Mar 06 2025
CAR-SPLASH identifies nascent pre-mRNA structures implicated in kinetic coupling and alternative splicing
Pre-mRNA splicing is kinetically coupled to transcription as shown by the widespread effects of transcription speed on alternative splicing outcomes. The molecular basis for such kinetic coupling is incompletely understood, but one potential mechanism is through elongation rate dependent alternative folding pathways of the nascent pre-mRNA. To search for RNA structures in nascent pre-mRNA, we modi...
Shenasa, H.
•
Fong, N.
•
Erickson, B.
•
Iosub, I.
...•
Bentley, D.
biorxiv
Thu Mar 06 2025
NOVEL CHARACTERISTICS OF SMALL NONCODING RNAS IN RAT EPIDIDYMAL EXTRACELLULAR PARTICLES
Extracellular vesicles (EVs) released from the epididymal epithelium, referred to as epididymosomes, impart functional competence on sperm as they transit the epididymis by merging with sperm and releasing a complex repertoire of molecules. The cargo of epididymal EVs includes small noncoding RNAs (sncRNAs) that are modified by external factors such as stress, nutrition, and drug use, which are de...
Gillette, R.
•
Sheinhaus, D. L.
•
Waghwala, S.
•
Gore, A. C.
biorxiv
Thu Mar 06 2025
Distinct allosteric networks in CDK4 and CDK6 in the cell cycle and in drug resistance
Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) are key regulators of the G1-S phase transition in the cell cycle. In cancer cells, CDK6 overexpression often outcompetes CDK4 in driving cell cycle progression, contributing to resistance against CDK4/6 inhibitors (CDK4/6i). This suggests distinct functional and conformational differences between these two kinases, despite their striking structural...
Zhang, W.
•
Bradburn, D.
•
Heidebrink, G.
•
Liu, Y.
...•
Koivomagi, M.
biorxiv
Wed Mar 05 2025
RNAprecis: Prediction of full-detail RNA conformation from the experimentally best-observed sparse parameters
We address the problem of predicting high detail RNA structure geometry from the information available in low resolution experimental maps of electron density. Here low resolution refers to [≥]2.5[A] where the location of the phosphate groups and the glyocosidic bonds can be determined from electron density but all other backbone atom positions cannot. In contrast, high resolution determines al...
Wiechers, H.
•
Williams, C. J.
•
Eltzner, B.
•
Hoppe, F.
...•
Huckemann, S. F.
biorxiv
Wed Mar 05 2025
A comprehensive survey and benchmark of deep learning-based methods for atomic model building from cryo-EM density maps
Advancements in deep learning (DL) have recently led to new methods for automated construction of atomic models of proteins, from single-particle cryogenic electron microscopy (cryo-EM) density maps. We conduct a comprehensive survey of these methods, distinguishing between direct model building approaches that only use density maps, and indirect ones that integrate sequence-to-structure predictio...
Zhang, C.
•
Condon, A.
•
Duc, K. D.