Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis
Rattachement africain : us, jp, ru. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, Plasmodium falciparum parasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin. Parasites also express a divergent heme oxygenase (HO)-like protein (PfHO) that lacks key active-site residues and has lost canonical HO activity. The cellular role of this unusual protein that underpins its retention by parasites has been unknown. To unravel PfHO function, we first determined a 2.8 Å-resolution X-ray structure that revealed a highly α-helical fold indicative of distant HO homology. Localization studies unveiled PfHO targeting to the apicoplast organelle, where it is imported and undergoes N-terminal processing but retains most of the electropositive transit peptide. We observed that conditional knockdown of PfHO was lethal to parasites, which died from defective apicoplast biogenesis and impaired isoprenoid-precursor synthesis. Complementation and molecular-interaction studies revealed an essential role for the electropositive N-terminus of PfHO, which selectively associates with the apicoplast genome and enzymes involved in nucleic acid metabolism and gene expression. PfHO knockdown resulted in a specific deficiency in levels of apicoplast-encoded RNA but not DNA. These studies reveal an essential function for PfHO in apicoplast maintenance and suggest that Plasmodium repurposed the conserved HO scaffold from its canonical heme-degrading function in the ancestral chloroplast to fulfill a critical adaptive role in organelle gene expression.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis
- Date Crossref
- 27/08/2024
- Éditeur
- eLife Sciences Publications, Ltd
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Utah Department of Biochemistry pays non établi dans la noticeUniversité ou école supérieure
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The University of Tokyo Department of Chemistry & Biotechnology pays non établi dans la noticeUniversité ou école supérieure
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Kyushu University pays non établi dans la noticeUniversité ou école supérieure
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Bioengineering Center pays non établi dans la noticeStructure de recherche
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University of California Department of Biological Chemistry pays non établi dans la noticeUniversité ou école supérieure
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Washington University School of Medicine Departments of Medicine and Molecular Microbiology pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Pharmaceutical Sciences Department of Protein Drug Discovery pays non établi dans la noticeUniversité ou école supérieure
Department of Biochemistry — University of Utah, Department of Chemistry & Biotechnology — The University of Tokyo et Kyushu University, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.