Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis DOI Creative Commons
Amanda Mixon Blackwell, Yasaman Jami‐Alahmadi, Armiyaw S. Nasamu

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 27, 2024

Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, Plasmodium falciparum internalize and digest abundant host hemoglobin 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) lacks key active-site residues has lost canonical HO activity. The cellular role this underpins its retention by been unknown. To unravel PfHO function, we first determined 2.8 Å-resolution X-ray structure revealed highly α-helical fold indicative distant homology. Localization studies unveiled targeting to apicoplast organelle, where it imported undergoes N-terminal processing but retains electropositive transit peptide. We observed conditional knockdown was lethal parasites, died from defective biogenesis impaired isoprenoid-precursor synthesis. Complementation molecular-interaction an essential N-terminus PfHO, selectively associates with genome enzymes involved in nucleic acid metabolism gene expression. resulted specific deficiency levels apicoplast-encoded RNA not DNA. These reveal function maintenance suggest repurposed conserved scaffold heme-degrading ancestral chloroplast fulfill critical adaptive organelle

Language: Английский

Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis DOI Creative Commons
Amanda Mixon Blackwell, Yasaman Jami‐Alahmadi, Armiyaw S. Nasamu

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 27, 2024

Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, Plasmodium falciparum internalize and digest abundant host hemoglobin 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) lacks key active-site residues has lost canonical HO activity. The cellular role this underpins its retention by been unknown. To unravel PfHO function, we first determined 2.8 Å-resolution X-ray structure revealed highly α-helical fold indicative distant homology. Localization studies unveiled targeting to apicoplast organelle, where it imported undergoes N-terminal processing but retains electropositive transit peptide. We observed conditional knockdown was lethal parasites, died from defective biogenesis impaired isoprenoid-precursor synthesis. Complementation molecular-interaction an essential N-terminus PfHO, selectively associates with genome enzymes involved in nucleic acid metabolism gene expression. resulted specific deficiency levels apicoplast-encoded RNA not DNA. These reveal function maintenance suggest repurposed conserved scaffold heme-degrading ancestral chloroplast fulfill critical adaptive organelle

Language: Английский

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