Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence

Diehl, Mathias; Weber, Sebastian; Cyrklaff, Marek; Sánchez, Cecilia P.; Beretta, Carlo A.; Roling, Lena; Simon, Caroline S.; Guizetti, Julien; Mayer, Matthias P.; Przyborski, Jude M.

doi:10.1101/2021.03.11.434953

Cited by 3 publications

(1 citation statement)

References 58 publications

(97 reference statements)

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“…It remains unclear whether J dots function as transporters of cholesterol or whether cholesterol aids in the stabilization of the transmembrane domains of the protein cargo [15,16,17,18]. The known protein components of J dots are present only in the Laveranian lineage and can be readily mutated without obvious effect on parasite growth in vitro, despite a significant alteration in the formation of knobs, adhesive structures at the surface of the infected erythrocyte [110].…”

Section: Cholesterol Transportersmentioning

confidence: 99%

Lipid transport proteins in malaria, from Plasmodium parasites to their hosts

Ressurreição

Ooij

2021

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Section: Cholesterol Transportersmentioning

confidence: 99%

Lipid transport proteins in malaria, from Plasmodium parasites to their hosts

Ressurreição

Ooij

2021

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans

Daniyan,

Singh,

Blatch

2024

IJMS

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Plasmodium knowlesi is a zoonotic form of human malaria, the pathology of which is poorly understood. While the J domain protein (JDP) family has been extensively studied in Plasmodium falciparum, and shown to contribute to malaria pathology, there is currently very limited information on the P. knowlesi JDPs (PkJDPs). This review provides a critical analysis of the literature and publicly available data on PkJDPs. Interestingly, the P. knowlesi genome encodes at least 31 PkJDPs, with well over half belonging to the most diverse types which contain only the signature J domain (type IIIs, 19) or a corrupted version of the J domain (type IVs, 2) as evidence of their membership. The more typical PkJDPs containing other domains typical of JDPs in addition to the J domain are much fewer in number (type IIs, 8; type Is, 2). This study indentifies PkJDPs that are potentially involved in: folding of newly synthesized or misfolded proteins within the P. knowlesi cytosol (a canonical type I and certain typical type IIs); protein translocation (a type III) and folding (a type II) in the ER; and protein import into mitochondria (a type III). Interestingly, a type II PkJDP is potentially exported to the host cell cytosol where it may recruit human HSP70 for the trafficking and folding of other exported P. knowlesi proteins. Experimental studies are required on this fascinating family of proteins, not only to validate their role in the pathology of knowlesi malaria, but also because they represent potential anti-malarial drug targets.

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Knobs, Adhesion, and Severe Falciparum Malaria

Wiser

2023

TropicalMed

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Plasmodium falciparum can cause a severe disease with high mortality. A major factor contributing to the increased virulence of P. falciparum, as compared to other human malarial parasites, is the sequestration of infected erythrocytes in the capillary beds of organs and tissues. This sequestration is due to the cytoadherence of infected erythrocytes to endothelial cells. Cytoadherence is primarily mediated by a parasite protein expressed on the surface of the infected erythrocyte called P. falciparum erythrocyte membrane protein-1 (PfEMP1). PfEMP1 is embedded in electron-dense protuberances on the surface of the infected erythrocytes called knobs. These knobs are assembled on the erythrocyte membrane via exported parasite proteins, and the knobs function as focal points for the cytoadherence of infected erythrocytes to endothelial cells. PfEMP1 is a member of the var gene family, and there are approximately 60 antigenically distinct PfEMP1 alleles per parasite genome. Var gene expression exhibits allelic exclusion, with only a single allele being expressed by an individual parasite. This results in sequential waves of antigenically distinct infected erythrocytes and this antigenic variation allows the parasite to establish long-term chronic infections. A wide range of endothelial cell receptors can bind to the various PfEMP1 alleles, and thus, antigenic variation also results in a change in the cytoadherence phenotype. The cytoadherence phenotype may result in infected erythrocytes sequestering in different tissues and this difference in sequestration may explain the wide range of possible clinical manifestations associated with severe falciparum malaria.

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Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence

Cited by 3 publications

References 58 publications

Lipid transport proteins in malaria, from Plasmodium parasites to their hosts

Lipid transport proteins in malaria, from Plasmodium parasites to their hosts

The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans

Knobs, Adhesion, and Severe Falciparum Malaria

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