The Role of Hsp70s in the Development and Pathogenicity of Plasmodium falciparum

Shonhai, Addmore

doi:10.1007/978-3-030-78397-6_3

Cited by 9 publications

(9 citation statements)

References 119 publications

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“… 85 As in the human system, PfHSP70-2 is proposed to interact with the ER-resident PfHSP40 homologous to Sec63 (PfSec63), and through its association with PfSec63 and the PfSec complex, to play a role in protein translocation into the ER. 11 , 80 , 86 , 87 , 88 Similarly to PfHSP70-x, PfHSP70-2 also interacts with exported virulence proteins such as P. falciparum erythrocyte membrane protein 1. 87 , 89 , 90 Very limited information about small molecule inhibitors of PfHSP70-2 is available.…”

Section: Malarial Hsps and Their Complexes As Drug Targetsmentioning

confidence: 99%

Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update

Ahmad,

Alhammadi,

Almaazmi

et al. 2024

Cell Stress and Chaperones

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Section: Malarial Hsps and Their Complexes As Drug Targetsmentioning

confidence: 99%

Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update

Ahmad,

Alhammadi,

Almaazmi

et al. 2024

Cell Stress and Chaperones

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“…Hsp70 is a molecular chaperone that is involved in several processes including protein folding, protein unfolding, assembly and disassembly of protein units, protein translocation, signal transduction, and DNA replication (Mayer and Bukau 2005 ; Shonhai 2021 ). Hsp70 function is further regulated by various post-transitional events such as cellular stress (heat stress, toxic and oxidative stress, heavy metals, and nutrient deficiency) (Rohland et al 2022 ).…”

Section: Association Of Hsp70 With the R2tp Complexmentioning

confidence: 99%

The multi-faceted roles of R2TP complex span across regulation of gene expression, translation, and protein functional assembly

Luthuli,

Shonhai

2023

Biophys Rev

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Macromolecular complexes play essential roles in various cellular processes. The assembly of macromolecular assemblies within the cell must overcome barriers imposed by a crowded cellular environment which is characterized by an estimated concentration of biological macromolecules amounting to 100–450 g/L that take up approximately 5–40% of the cytoplasmic volume. The formation of the macromolecular assemblies is facilitated by molecular chaperones in cooperation with their co-chaperones. The R2TP protein complex has emerged as a co-chaperone of Hsp90 that plays an important role in macromolecular assembly. The R2TP complex is composed of a heterodimer of RPAP3:P1H1DI that is in turn complexed to members of the ATPase associated with diverse cellular activities (AAA +), RUVBL1 and RUVBL2 (R1 and R2) families. What makes the R2TP co-chaperone complex particularly important is that it is involved in a wide variety of cellular processes including gene expression, translation, co-translational complex assembly, and posttranslational protein complex formation. The functional versatility of the R2TP co-chaperone complex makes it central to cellular development; hence, it is implicated in various human diseases. In addition, their roles in the development of infectious disease agents has become of interest. In the current review, we discuss the roles of these proteins as co-chaperones regulating Hsp90 and its partnership with Hsp70. Furthermore, we highlight the structure–function features of the individual proteins within the R2TP complex and describe their roles in various cellular processes.

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“…P. falciparum has only six Hsp70s (PfHsp70s; Shonhai et al, 2007 ; Shonhai, 2021 ) and four Hsp90s (PfHsp90s; Shahinas and Pillai, 2021 ). However, there is a highly expanded complement of JDPs, with 49 members (PfJDPs; Botha et al, 2007 ; Njunge et al, 2013 ; Pesce and Blatch, 2014 ; Dutta et al, 2021a ).…”

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

confidence: 99%

“…In the endoplasmic reticulum (ER), there are two Hsp70s, PfHsp70-2 (a BiP/Grp78 homologue) and PfHsp70-y (a Hsp110/Grp170 homologue). PfHsp70-2 is essential ( Zhang et al, 2018 ), and has been proposed to be involved in protein translocation into the ER, working with a PfJDP (PfSec63) and the PfSec translocon ( Tuteja, 2007 ; Blatch and Zimmermann, 2009 ; Cortés et al, 2020 ; Shonhai, 2021 ). PfHsp70-2 was found to functionally associate with another PfJDP (Pfj2) and a protein disulfide isomerase (PDI-8) in the oxidative folding of ER proteins ( Cobb et al, 2017 ).…”

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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The Role of Hsp70s in the Development and Pathogenicity of Plasmodium falciparum

Cited by 9 publications

References 119 publications

Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update

Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update

The multi-faceted roles of R2TP complex span across regulation of gene expression, translation, and protein functional assembly

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

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