Tawanda Zininga

Stellenbosch University | SUN · Department of Biochemistry

Plasmodium falciparum expresses four heat shock protein 90 (Hsp90) members. Among these, one, glucose‐regulated protein 94 ( Pf Grp94), is localized in the endoplasmic reticulum (ER). Both the cytosolic and ER‐based Hsp90s are essential for parasite survival under all growth conditions. The cytosolic version has been extensively studied and has bee...

Plasmodium falciparum heat shock protein 70-1 (PfHsp70-1) and PfHsp70-z are essential cytosol localised chaperones of the malaria parasite. The two chaperones functionally interact to drive folding of several parasite proteins. While PfHsp70-1 is regarded as a canonical Hsp70 chaperone, PfHsp70-z belongs to the Hsp110 subcluster. One of the distinc...

Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, an...

Plasmodium falciparum, the predominant cause of severe malaria, thrives within both poikilotherm mosquitoes and homeotherm humans, navigating challenging temperature shifts during its life cycle. Survival in such varying environments necessitate the development of robust mechanisms, including a sophisticated protein folding system to mitigate prote...

Simple Summary Breast cancer is a global burden with the most severe subtype being triple negative breast cancer (TNBC). Despite advances in conventional therapies, treatment for TNBC is currently lacking. Interestingly, cholesterol has gained interest as a potential therapeutic target due to cancer cells’ increased reliance on this macromolecule....

Cell surface-bound human Hsp70 (hHsp70) sensitises tumour cells to the cytolytic attack of natural killer (NK) cells through the mediation of apoptosis-inducing serine protease, granzyme B (GrB). hHsp70 is thought to recruit NK cells to the immunological synapse via the extracellularly exposed 14 amino acid sequence, TKDNNLLGRFELSG, known as the TK...

Although protein interaction studies are instrumental in understanding protein networks, most protein interaction techniques depend on use of sophisticated and expensive equipment. This makes it difficult for under-resourced laboratories to conduct protein–protein interaction studies. As such, we sought to explore the prospects of using ELISA and s...

Plasmodium falciparum Hsp70-1 (PfHsp70-1; PF3D7_0818900) and PfHsp90 (PF3D7_0708400) are essential cytosol localized chaperones of the malaria parasite. The two chaperones form a functional complex via the adaptor protein, Hsp90-Hsp70 organizing protein (PfHop [PF3D7_1434300]), which modulates the interaction of PfHsp70-1 and PfHsp90 through its te...

The coronavirus disease (COVID-19) caused by a coronavirus identified in December 2019 has caused a global pandemic. COVID-19 was declared a pandemic in March 2020 and has led to more than 6.3 million deaths. The pandemic has disrupted world travel, economies, and lifestyles worldwide. Although vaccination has been an effective tool to reduce the s...

Malaria is still one of the major killer parasitic diseases in tropical settings, posing a public health threat. The development of antimalarial drug resistance is reversing the gains made in attempts to control the disease. The parasite leads a complex life cycle that has adapted to outwit almost all known antimalarial drugs to date, including the...

Malaria is one of the major parasitic killer diseases worldwide. Severe cases of malaria are mostly in children under the age of 5 years due to their naïve immune system and in pregnant women with weakened immune responses. Inflammatory immune responses against the parasite involve complement activation as well as the antibody and effector cell-med...

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. To date, no reliable biomarkers or therapeutic interventions for the condition exist, thus necessitating an urgent need for identification of novel PPCM drug target...

Here, we present data on characterisation of the linker of Plasmodium falciparum Hsp110 (PfHsp70-z) relative to the linker of canonical Hsp70s in support of a co-published article [1]. The linker of PfHsp70-z was switched with that of canonical Hsp70s, represented by PfHsp70-1 (cytosolic counterpart of PfHsp70-z) and E. coli Hsp70/DnaK. The dataset...

Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed. In line with this, we designed and synthesised a series of novel N-(7-chloroquinolin-4-yl)-N'-(4,6-diphenylpyrim...

Plasmodium falciparum expresses two essential cytosol localised chaperones; PfHsp70-1 and PfHsp70-z. PfHsp70-z (Hsp110 homologue) is thought to facilitate nucleotide exchange function of PfHsp70-1. PfHsp70-1 is a refoldase, while PfHsp70-z is restricted to holdase chaperone function. The structural features delineating functional specialisation of...

Parasitic organisms especially those of the Apicomplexan phylum, harbour a cytosol localised canonical Hsp70 chaperone. One of the defining features of this protein is the presence of GGMP repeat residues sandwiched between α-helical lid and C-terminal EEVD motif. The role of the GGMP repeats of Hsp70s remains unknown. In the current study, we intr...

Glioblastoma multiforme (GBM) is an aggressive grade IV primary malignant tumour which accounts for 78 % of all brain tumours. K0513 is a GBM biomarker that is upregulated in the invasive phenotype. K0513 is expressed ubiquitously and is reportedly enriched in the cerebral cortex of the brain. K0513 is further implicated in signalling pathways invo...

Hsp70 is a conserved molecular chaperone. How Hsp70 exhibits specialized functions across species remains to be understood. Plasmodium falciparum Hsp70-1 (PfHsp70-1) and Escherichia coli DnaK are cytosol localized molecular chaperones that are important for the survival of these two organisms. In the current study, we investigated comparative struc...

Plasmodium falciparum causes the most lethal form of malaria. The cooperation of heat shock protein (Hsp) 70 and 90 is thought to facilitate folding of select group of cellular proteins that are crucial for cyto-protection and development of the parasites. Hsp70 and Hsp90 are brought into a functional complex that allows substrate exchange by stres...

Hsp70 is one of the most prominent molecular chaperones. Although Hsp70s from various organisms are generally conserved, they exhibit specialised cellular functions. It remains to be fully understood how these highly conserved molecules exhibit specialised functional features. Plasmodium falciparum Hsp70-1 (PfHsp70-1) is a cytosol localised molecul...

Plasmodium falciparum causes the most lethal form of malaria. The cooperation of heat shock protein (Hsp) 70 and 90 is important for folding of a select number of cellular proteins that are crucial for cyto-protection and development of the parasites. Hsp70 and Hsp90 are brought into a functional complex that allows substrate exchange by stress ind...

Obligate protozoan parasites of the kinetoplastids and apicomplexa infect human cells to complete their life cycles. Some of the members of these groups of parasites develop in at least two systems, the human host and the insect vector. Survival under the varied physiological conditions associated with the human host and in the arthropod vectors re...

The heat shock 70 (Hsp70) family of molecular chaperones plays a central role in maintaining cellular proteostasis. Structurally, Hsp70s are composed of an N-terminal nucleotide binding domain (NBD) which exhibits ATPase activity, and a C-terminal substrate binding domain (SBD). The binding of ATP at the NBD and its subsequent hydrolysis influences...

The heat shock protein 70 (Hsp70) family of molecular chaperones are crucial for the survival and pathogenicity of the main agent of malaria, Plasmodium falciparum. Hsp70 is central to cellular proteostasis and some of its isoforms are essential for survival of the malaria parasite. In addition, they are also implicated in the development of antima...

Heat shock proteins (Hsps) are conserved molecules whose main role is to facilitate folding of other proteins. Most Hsps are generally stress-inducible as they play a particularly important cytoprotective role in cells exposed to stressful conditions. Initially, Hsps were generally thought to occur intracellulary. However, recent work has shown tha...

Supplementary Figure 1 Expression and purification of recombinant proteins Supplementary Figure 2 PfHsp70‐x directly interacts with human Hop

Supplementary Table 1 Binding affinities of PfHsp70‐x/PfHsp70‐xT for peptide substrates

Plasmodium falciparum, the main agent of malaria expresses six members of the heat shock protein 70 (Hsp70) family. Hsp70s serve as protein folding facilitators in the cell. Amongst the six Hsp70 species that P. falciparum expresses, Hsp70‐x (PfHsp70‐x), is partially exported to the host red blood cell where it is implicated in host cell remodeling...

Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70 family of proteins represents one of the most important molecular chaperones in the cell. Plasmodium falciparum, the main agent of malaria, expresses six Hsp70 isoforms. Two (PfHsp70-1 and...

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of two plants, Pterocarpus angolensis and Ziziphus mu...

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of two plants, Pterocarpus angolensis and Ziziphus mu...

Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in cellular proteostasis. Hsp70s are also implicated in the survival and pathogenicity of malaria parasites. The main agent of malaria, Plasmodium falciparum, expresses six Hsp70s. Of these, two (PfHsp70-1 and PfHsp70-z) localize to the parasite cytosol. Previously...

Oxidative stress has been implicated in the damage of biological molecules resulting in aging and diseases such as Alzheimer, cancer, diabetes, cardiovascular disorders. The study aimed at determining the phenolic contents and antioxidant activities of Pterocarpus angolensis crude extract and fractions. The crude extract and fractions of P. angolen...

Background The Vhembe region of the Limpopo province has a rich tradition of medicinal plants use. Traditionally, boiled roots of Ziziphus mucronata are used in the treatment of boils, general swelling and other skin infections. A combination of leaf paste and root infusion treats measles, dysentery, chest complains, and gland swelling. Pterocarpus...

S-adenosylmethionine decarboxylase (PfAdoMetDC) from Plasmodium falciparum is a prospective antimalarial drug target. The production of recombinant PfAdoMetDC for biochemical validation as a drug target is important. The production of PfAdoMetDC in Escherichia coli has been reported to result in unsatisfactory yields and poor quality product. The c...

Sequence alignment of PfHsp70 and E. coli DnaK. Sequence alignment of E. coli DnaK (accession number: BAA01595.1) and PfHsp70 (accession number: PF08_0054) were conducted using ClustalW and Boxshade. The following structural features are highlighted: the highly conserved linker segment (black horizontal line) which separates the ATPase domain from...

Description of primers used towards generation of destination plasmids. (DOCX)

KPf and PfHsp70 do not co-purify with PfAdoMetDC. Western blot representing the purification of PfAdoMetDC expressed in E. coli BL21 (DE3) Star cells rehosted with various chaperone combinations. Lanes: U–PfAdoMetDC expressed in the absence of supplemented chaperones; K–PfAdoMetDC co-expressed with supplemented DnaK; KPf–PfAdoMetDC expressed in cel...

E. coli strains and plasmids used in this study. (DOCX)

The role of molecular chaperones, among them heat shock proteins (Hsps), in the development of malaria parasites has been well documented. Hsp70s are molecular chaperones that facilitate protein folding. Hsp70 proteins are composed of an N-terminal nucleotide binding domain (NBD), which confers them with ATPase activity and a C-terminal substrate b...

Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red...

Six Hsp70-like genes are represented on the genome of Plasmodium falciparum. Of these two occur in the cytosol: P. falciparum Hsp70-z (PfHsp70-z) and PfHsp70-1. PfHsp70-1 is a well characterised canonical Hsp70 that facilitates protein quality control and is crucial for the development of malaria parasites. There is very little known about PfHsp70-...

Heat shock proteins (Hsps) are ubiquitous and conserved molecules whose main function is to facilitate protein folding (molecular chaperone function). Some Hsps such as Hsp70 are also involved in protein folding, protein trafficking and ubiquitination of misfolded protein to facilitate their degradation. Hsps occur in functional networks and hence...