Plasmodium, the Apicomplexa Outlier When It Comes to Protein Synthesis DOI Creative Commons
José R. Jaramillo Ponce, Magali Frugier

Biomolecules, Journal Year: 2023, Volume and Issue: 14(1), P. 46 - 46

Published: Dec. 29, 2023

Plasmodium is an obligate intracellular parasite that has numerous interactions with different hosts during its elaborate life cycle. This also the case for other parasites belonging to same phylum Apicomplexa. In this study, we bioinformatically identified components of multi-synthetase complexes (MSCs) several Apicomplexa and modelled their assembly using AlphaFold2. It appears none these MSCs resemble two have characterized in Plasmodium. Indeed, tRip, central protein involved association from homologues, suggesting tRip-dependent import exogenous tRNAs not conserved apicomplexan parasites. Based on observation, searched obvious differences could explain singularity synthesis by comparing tRNA genes amino acid usage genomes. We noted a contradiction between large number asparagine residues used proteomes single gene encoding inserts them into proteins. observation remains true all Plasmodia strains studied, even those do contain long homorepeats.

Language: Английский

A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites DOI Creative Commons
Michael Foley, Dimuthu Angage, Robin F. Anders

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Abstract Broadly cross-reactive anti-malarial vaccines and therapeutic interventions are needed to achieve better outcomes in controlling and, eventually, eradicating malaria. Apical membrane antigen-1 (AMA1) is a structurally functionally conserved malarial vaccine candidate involved the tight junction formation with rhoptry neck protein (RON) complex at host cell-parasite interface. This interaction crucial for all Plasmodium parasites invade human erythrocytes, hepatocytes mosquito salivary glands effectively. However, extensive surface polymorphisms have induced P. falciparum strain-specific protection which has so far hindered progression of AMA1-based beyond first clinical trial. Here, we identified humanised single-domain (i-body) that recognises pan-species conformational epitope AMA1 low nanomolar affinity inhibits binding RON2 ligand AMA1. Structural characterisation indicated WD34 i-body engages centre hydrophobic cleft AMA1, where interacting residues highly among species other apicomplexans. Further, showed merozoite invasion into RBCs by multiple Plasmodium species hepatocyte sporozoites. Our work describes identification biologic high multi-lifecycle stage inhibitory activity. identifies new tools species-independent immunoprophylaxis possible target structure-based development against

Language: Английский

Citations

1

Plasmodium, theApicomplexaoutlier when it comes to protein synthesis DOI Open Access
José R. Jaramillo Ponce, Magali Frugier

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 10, 2023

ABSTRACT Plasmodium is an obligate intracellular parasite that makes numerous interactions with different hosts during its elaborate life cycle. This also the case for other parasites belong to same phylum Apicomplexa . In this study, we identified bioinformatically components of multi-synthetase complexes (MSC) several parasites. By using AlphaFold2 modeling compare their assembly, it appears none these MSCs resemble those in particular, discrepancies between core complexes, tRip and homologs indicate tRip-dependent exogenous tRNA import not conserved Based on observation, looked obvious differences could explain singularity The content genes amino acid usage genomes highlighted originality Plasmodia translation. evident respect asparagine acid, which highly used proteomes, scarcity Asn required protein synthesis, regardless long homorepeats or AT genomes.

Language: Английский

Citations

0

Transcriptomic approaches for identifying potential transmission blocking vaccine candidates in Plasmodium falciparum: a review of current knowledge and future directions DOI Creative Commons
Gutthedhar Varijakshi, Mallya Divya, Akshay Pramod Ware

et al.

3 Biotech, Journal Year: 2023, Volume and Issue: 13(10)

Published: Sept. 12, 2023

Abstract Utilizing transcriptomics, promising methods for identifying unique genes associated with Plasmodium gametocyte development offer a potential avenue novel candidate targets in transmission blocking vaccine development. In this review, we identified 40 publicly available transcriptomic datasets related to parasite factors linked sexual stage transmission, from which analyzed two RNA-Seq identify crucial the of P. falciparum humans mosquito vectors. Differential expression analysis revealed 3500 (2489 upregulated and 1011 downregulated) common differentially expressed throughout occurring both (gametocyte II, V) mosquitoes (ookinete). Among 1283 (914 369 826 (719 107 were specific female male gametocytes, respectively. Also, 830 transition that may be involved adaptation survival between human stages. Additionally, reviewed functional aspects important highly pathway evaluated their suitability as candidates. The review provides researchers insight into importance critical markers aid rational strategies.

Language: Английский

Citations

0

Plasmodium, the Apicomplexa Outlier When It Comes to Protein Synthesis DOI Creative Commons
José R. Jaramillo Ponce, Magali Frugier

Biomolecules, Journal Year: 2023, Volume and Issue: 14(1), P. 46 - 46

Published: Dec. 29, 2023

Plasmodium is an obligate intracellular parasite that has numerous interactions with different hosts during its elaborate life cycle. This also the case for other parasites belonging to same phylum Apicomplexa. In this study, we bioinformatically identified components of multi-synthetase complexes (MSCs) several Apicomplexa and modelled their assembly using AlphaFold2. It appears none these MSCs resemble two have characterized in Plasmodium. Indeed, tRip, central protein involved association from homologues, suggesting tRip-dependent import exogenous tRNAs not conserved apicomplexan parasites. Based on observation, searched obvious differences could explain singularity synthesis by comparing tRNA genes amino acid usage genomes. We noted a contradiction between large number asparagine residues used proteomes single gene encoding inserts them into proteins. observation remains true all Plasmodia strains studied, even those do contain long homorepeats.

Language: Английский

Citations

0