Structural insights into the binding mechanism of Plasmodium falciparum exported Hsp40-Hsp70 chaperone pair

Behl, Ankita; Mishra, Prakash Chandra

doi:10.1016/j.compbiolchem.2019.107099

Cited by 14 publications

(5 citation statements)

References 62 publications

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“…However, it is also likely that the full-length PfJDPs contain regions beyond the J domain that determine co-chaperone-chaperone specificity. This interpretation is consistent with structural analyses of the interaction between PFA0660w and PfHsp70-x, which indicated that they associated in a bipartite manner requiring both the J domain and the G/F region of PFA0660w ( Behl and Mishra 2019 ).…”

Section: J Dots In the Host Cytosol Contain Pfjdps And Pfhsp70-xsupporting

confidence: 86%

Exported J domain proteins of the human malaria parasite

Almaazmi

Singh

Dutta

et al. 2022

Front. Mol. Biosci.

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The heat shock protein 40 (Hsp40) family, also called J domain proteins (JDPs), regulate their Hsp70 partners by ensuring that they are engaging the right substrate at the right time and in the right location within the cell. A number of JDPs can serve as co-chaperone for a particular Hsp70, and so one generally finds many more JDPs than Hsp70s in the cell. In humans there are 13 Hsp70s and 49 JDPs. The human malaria parasite, Plasmodium falciparum, has dedicated an unusually large proportion of its genome to molecular chaperones, with a disproportionately high number of JDPs (PfJDPs) of 49 members. Interestingly, just under half of the PfJDPs are exported into the host cell during the asexual stage of the life cycle, when the malaria parasite invades mature red blood cells. Recent evidence suggests that these PfJDPs may be functionalizing both host and parasite Hsp70s within the infected red blood cell, and thereby driving the renovation of the host cell towards pathological ends. PfJDPs have been found to localize to the host cytosol, mobile structures within the host cytosol (so called “J Dots”), the host plasma membrane, and specialized structures associated with malaria pathology such as the knobs. A number of these exported PfJDPs are essential, and there is growing experimental evidence that they are important for the survival and pathogenesis of the malaria parasite. This review critiques our understanding of the important role these exported PfJDPs play at the host-parasite interface.

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Section: J Dots In the Host Cytosol Contain Pfjdps And Pfhsp70-xsupporting

confidence: 86%

Exported J domain proteins of the human malaria parasite

Almaazmi

Singh

Dutta

et al. 2022

Front. Mol. Biosci.

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“…HSPs, including Hsp70 and Hsp90, have been identified as potential drug targets in parasites such as P. falciparum and A. terreus [ 180 , 181 ]. Studies targeting the Hsp90–calcineurin pathway against several pathogenic fungal species have been performed using the calcineurin inhibitors Cyclosporine A and FK506 (tacrolimus), Hsp90 inhibitor Geldanamycin and its derivatives, and Trichostatin A, which inhibits Hsp90 function by inducing Hsp90 acetylation [ 16 ].…”

Section: Antifungal Therapymentioning

confidence: 99%

Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections

Neves-da-Rocha,

Santos-Saboya,

Lopes

et al. 2023

Microorganisms

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Fungi are a diverse group of eukaryotic organisms that infect humans, animals, and plants. To successfully colonize their hosts, pathogenic fungi must continuously adapt to the host’s unique environment, e.g., changes in temperature, pH, and nutrient availability. Appropriate protein folding, assembly, and degradation are essential for maintaining cellular homeostasis and survival under stressful conditions. Therefore, the regulation of proteostasis is crucial for fungal pathogenesis. The heat shock response (HSR) is one of the most important cellular mechanisms for maintaining proteostasis. It is activated by various stresses and regulates the activity of heat shock proteins (HSPs). As molecular chaperones, HSPs participate in the proteostatic network to control cellular protein levels by affecting their conformation, location, and degradation. In recent years, a growing body of evidence has highlighted the crucial yet understudied role of stress response circuits in fungal infections. This review explores the role of protein homeostasis and HSPs in fungal pathogenicity, including their contributions to virulence and host–pathogen interactions, as well as the concerted effects between HSPs and the main proteostasis circuits in the cell. Furthermore, we discuss perspectives in the field and the potential for targeting the components of these circuits to develop novel antifungal therapies.

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“…PfHsp70-x is the only exported member of the PfHsp70 family, and has been shown to be localized to the PV and erythrocyte cytosol where it is found free or associated with PfJDPs (PFE0055c and PFA0660w) in mobile lipid containing complexes called J-Dots ( Külzer et al, 2012 ; Grover et al, 2013 ; Behl and Mishra. 2019 ).…”

Section: Pfhsp70s Are the Guardians Of The Parasite-resident And Expo...mentioning

confidence: 99%

Plasmodium falciparum Molecular Chaperones: Guardians of the Malaria Parasite Proteome and Renovators of the Host Proteome

Blatch

2022

Front. Cell Dev. Biol.

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Plasmodium falciparum is a unicellular protozoan parasite and causative agent of the most severe form of malaria in humans. The malaria parasite has had to develop sophisticated mechanisms to preserve its proteome under the changing stressful conditions it confronts, particularly when it invades host erythrocytes. Heat shock proteins, especially those that function as molecular chaperones, play a key role in protein homeostasis (proteostasis) of P. falciparum. Soon after invading erythrocytes, the malaria parasite exports a large number of proteins including chaperones, which are responsible for remodeling the infected erythrocyte to enable its survival and pathogenesis. The infected host cell has parasite-resident and erythrocyte-resident chaperones, which appear to play a vital role in the folding and functioning of P. falciparum proteins and potentially host proteins. This review critiques the current understanding of how the major chaperones, particularly the Hsp70 and Hsp40 (or J domain proteins, JDPs) families, contribute to proteostasis of the malaria parasite-infected erythrocytes.

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Structural insights into the binding mechanism of Plasmodium falciparum exported Hsp40-Hsp70 chaperone pair

Cited by 14 publications

References 62 publications

Exported J domain proteins of the human malaria parasite

Exported J domain proteins of the human malaria parasite

Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections

Plasmodium falciparum Molecular Chaperones: Guardians of the Malaria Parasite Proteome and Renovators of the Host Proteome

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