Challenges and curriculum transformation in the higher education sector in South Africa: a case study in WASH to improve the training of pharmacists
- Tandlich, Roman, Ngqwala, Nosiphiwe P, Boshoff, Aileen, Madikizela, Phindile, Srinivas, Sunitha C, Pyle, Desmond M, Oosthuizen, Rene
- Authors: Tandlich, Roman , Ngqwala, Nosiphiwe P , Boshoff, Aileen , Madikizela, Phindile , Srinivas, Sunitha C , Pyle, Desmond M , Oosthuizen, Rene
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/76858 , vital:30631 , https://doi.org/10.2478/atd-2018-0001
- Description: South Africa is a member state of the “BRICS” bloc (BRICS2017.org, 2017) and the G20 group of the 20 nations/economic blocs, which between them account for the majority of the world’s trade and economic activity. It faces many developmental challenges which are mirrored in its higher education sector. In this article, the authors seek to provide an overview of the challenges that South African higher education faces in the achievement of the developmental goals of the country. The focus of this paper is a case study in WASH (water, sanitation and hygiene) to improve context-specific responses that trains pharmacists on knowledge and skills.
- Full Text:
- Date Issued: 2018
- Authors: Tandlich, Roman , Ngqwala, Nosiphiwe P , Boshoff, Aileen , Madikizela, Phindile , Srinivas, Sunitha C , Pyle, Desmond M , Oosthuizen, Rene
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/76858 , vital:30631 , https://doi.org/10.2478/atd-2018-0001
- Description: South Africa is a member state of the “BRICS” bloc (BRICS2017.org, 2017) and the G20 group of the 20 nations/economic blocs, which between them account for the majority of the world’s trade and economic activity. It faces many developmental challenges which are mirrored in its higher education sector. In this article, the authors seek to provide an overview of the challenges that South African higher education faces in the achievement of the developmental goals of the country. The focus of this paper is a case study in WASH (water, sanitation and hygiene) to improve context-specific responses that trains pharmacists on knowledge and skills.
- Full Text:
- Date Issued: 2018
Localisation of Theiler's murine encephalomyelitis virus protein 2C to the golgi apparatus using antibodies generated against a peptide region:
- Jauka, Tembisa, Mutsvunguma, Lorraine Z, Boshoff, Aileen, Edkins, Adrienne L, Knox, Caroline M
- Authors: Jauka, Tembisa , Mutsvunguma, Lorraine Z , Boshoff, Aileen , Edkins, Adrienne L , Knox, Caroline M
- Date: 2010
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165074 , vital:41206 , DOI: 10.1016/j.jviromet.2010.05.009
- Description: The picornavirus 2C protein is highly conserved and indispensible for virus replication. Polyclonal antibodies against Theiler's murine encephalomyelitis virus (TMEV) 2C protein were generated by immunisation of rabbits with a peptide comprising amino acids 31–210 of the protein. Antibodies were used to investigate the localisation of 2C in infected cells by indirect immunofluorescence and confocal microscopy. Analysis of infected cells revealed that the distribution of 2C changed during infection.
- Full Text:
- Date Issued: 2010
- Authors: Jauka, Tembisa , Mutsvunguma, Lorraine Z , Boshoff, Aileen , Edkins, Adrienne L , Knox, Caroline M
- Date: 2010
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165074 , vital:41206 , DOI: 10.1016/j.jviromet.2010.05.009
- Description: The picornavirus 2C protein is highly conserved and indispensible for virus replication. Polyclonal antibodies against Theiler's murine encephalomyelitis virus (TMEV) 2C protein were generated by immunisation of rabbits with a peptide comprising amino acids 31–210 of the protein. Antibodies were used to investigate the localisation of 2C in infected cells by indirect immunofluorescence and confocal microscopy. Analysis of infected cells revealed that the distribution of 2C changed during infection.
- Full Text:
- Date Issued: 2010
The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum
- Shonhai, Addmore, Boshoff, Aileen, Blatch, Gregory L
- Authors: Shonhai, Addmore , Boshoff, Aileen , Blatch, Gregory L
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6486 , http://hdl.handle.net/10962/d1006269 , http://dx.doi.org/10.1110/ps.072918107
- Description: It is becoming increasingly apparent that heat shock proteins play an important role in the survival of Plasmodium falciparum against temperature changes associated with its passage from the cold-blooded mosquito vector to the warm-blooded human host. Interest in understanding the possible role of P. falciparum Hsp70s in the life cycle of the parasite has led to the identification of six HSP70 genes. Although most research attention has focused primarily on one of the cytosolic Hsp70s (PfHsp70-1) and its endoplasmic reticulum homolog (PfHsp70-2), further functional insights could be inferred from the structural motifs exhibited by the rest of the Hsp70 family members of P. falciparum. There is increasing evidence that suggests that PfHsp70-1 could play an important role in the life cycle of P. falciparum both as a chaperone and immunogen. In addition, P. falciparum Hsp70s and Hsp40 partners are implicated in the intracellular and extracellular trafficking of proteins. This review summarizes data emerging from studies on the chaperone role of P. falciparum Hsp70s, taking advantage of inferences gleaned from their structures and information on their cellular localization. The possible associations between P. falciparum Hsp70s with their cochaperone partners as well as other chaperones and proteins are discussed.
- Full Text:
- Date Issued: 2007
- Authors: Shonhai, Addmore , Boshoff, Aileen , Blatch, Gregory L
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6486 , http://hdl.handle.net/10962/d1006269 , http://dx.doi.org/10.1110/ps.072918107
- Description: It is becoming increasingly apparent that heat shock proteins play an important role in the survival of Plasmodium falciparum against temperature changes associated with its passage from the cold-blooded mosquito vector to the warm-blooded human host. Interest in understanding the possible role of P. falciparum Hsp70s in the life cycle of the parasite has led to the identification of six HSP70 genes. Although most research attention has focused primarily on one of the cytosolic Hsp70s (PfHsp70-1) and its endoplasmic reticulum homolog (PfHsp70-2), further functional insights could be inferred from the structural motifs exhibited by the rest of the Hsp70 family members of P. falciparum. There is increasing evidence that suggests that PfHsp70-1 could play an important role in the life cycle of P. falciparum both as a chaperone and immunogen. In addition, P. falciparum Hsp70s and Hsp40 partners are implicated in the intracellular and extracellular trafficking of proteins. This review summarizes data emerging from studies on the chaperone role of P. falciparum Hsp70s, taking advantage of inferences gleaned from their structures and information on their cellular localization. The possible associations between P. falciparum Hsp70s with their cochaperone partners as well as other chaperones and proteins are discussed.
- Full Text:
- Date Issued: 2007
General structural and functional features of molecular chaperones:
- Edkins, Adrienne L, Boshoff, Aileen
- Authors: Edkins, Adrienne L , Boshoff, Aileen
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164808 , vital:41174 , ISBN 978-94-007-7437-7 , DOI: 10.1007/978-94-007-7438-4_2
- Description: Molecular chaperones are a group of structurally diverse and highly conserved ubiquitous proteins. They play crucial roles in facilitating the correct folding of proteins in vivo by preventing protein aggregation or facilitating the appropriate folding and assembly of proteins. Heat shock proteins form the major class of molecular chaperones that are responsible for protein folding events in the cell. This is achieved by ATP-dependent (folding machines) or ATP-independent mechanisms (holders). Heat shock proteins are induced by a variety of stresses, besides heat shock. The large and varied heat shock protein class is categorised into several subfamilies based on their sizes in kDa namely, small Hsps (HSPB), Hsp40 (DNAJ), Hsp60 (HSPD/E; Chaperonins), Hsp70 (HSPA), Hsp90 (HSPC), and Hsp100.
- Full Text:
- Date Issued: 2014
- Authors: Edkins, Adrienne L , Boshoff, Aileen
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/164808 , vital:41174 , ISBN 978-94-007-7437-7 , DOI: 10.1007/978-94-007-7438-4_2
- Description: Molecular chaperones are a group of structurally diverse and highly conserved ubiquitous proteins. They play crucial roles in facilitating the correct folding of proteins in vivo by preventing protein aggregation or facilitating the appropriate folding and assembly of proteins. Heat shock proteins form the major class of molecular chaperones that are responsible for protein folding events in the cell. This is achieved by ATP-dependent (folding machines) or ATP-independent mechanisms (holders). Heat shock proteins are induced by a variety of stresses, besides heat shock. The large and varied heat shock protein class is categorised into several subfamilies based on their sizes in kDa namely, small Hsps (HSPB), Hsp40 (DNAJ), Hsp60 (HSPD/E; Chaperonins), Hsp70 (HSPA), Hsp90 (HSPC), and Hsp100.
- Full Text:
- Date Issued: 2014
The biotransformation of phenolic pollutants using polyphenol oxidase
- Authors: Boshoff, Aileen
- Date: 2002
- Subjects: Polyphenol oxidase Sewage -- Purification
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3976 , http://hdl.handle.net/10962/d1004035
- Description: The potential of using mushroom polyphenol oxidase (EC 1.14.18.1) as a biocatalyst for the biotransformation of phenols to produce catechols in an aqueous medium was investigated. Polyphenol oxidase is characterised by two distinct reactions i.e., the ortho-hydroxylation of phenols to catechols (cresolase activity) and the subsequent oxidation of catechols to orthoquinones (catecholase activity). In order to facilitate the development of a process to produce catechols, the accumulation of catechol as a true intermediate product released in the reaction system needed to be investigated, as its release had been disputed due to the oxidation of catechols to o-quinones. Using LC-MS, catechol products were successfully identified as true intermediate products formed during biocatalytic reactions in water.
- Full Text:
- Date Issued: 2002
- Authors: Boshoff, Aileen
- Date: 2002
- Subjects: Polyphenol oxidase Sewage -- Purification
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3976 , http://hdl.handle.net/10962/d1004035
- Description: The potential of using mushroom polyphenol oxidase (EC 1.14.18.1) as a biocatalyst for the biotransformation of phenols to produce catechols in an aqueous medium was investigated. Polyphenol oxidase is characterised by two distinct reactions i.e., the ortho-hydroxylation of phenols to catechols (cresolase activity) and the subsequent oxidation of catechols to orthoquinones (catecholase activity). In order to facilitate the development of a process to produce catechols, the accumulation of catechol as a true intermediate product released in the reaction system needed to be investigated, as its release had been disputed due to the oxidation of catechols to o-quinones. Using LC-MS, catechol products were successfully identified as true intermediate products formed during biocatalytic reactions in water.
- Full Text:
- Date Issued: 2002
Cytosolic and ER J-domains of mammalian and parasitic origin can functionally interact with DnaK
- Nicoll, W S, Botha, M, McNamara, Caryn, Schlange, M, Pesce, E R, Boshoff, Aileen, Ludewig, M H, Zimmerman, R, Cheetham, M E, Chapple, J P, Blatch, Gregory L
- Authors: Nicoll, W S , Botha, M , McNamara, Caryn , Schlange, M , Pesce, E R , Boshoff, Aileen , Ludewig, M H , Zimmerman, R , Cheetham, M E , Chapple, J P , Blatch, Gregory L
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6484 , http://hdl.handle.net/10962/d1006261 , http://www.sciencedirect.com/science/article/pii/S1357272506003268
- Description: Both prokaryotic and eukaryotic cells contain multiple heat shock protein 40 (Hsp40) and heat shock protein 70 (Hsp70) proteins, which cooperate as molecular chaperones to ensure fidelity at all stages of protein biogenesis. The Hsp40 signature domain, the J-domain, is required for binding of an Hsp40 to a partner Hsp70, and may also play a role in the specificity of the association. Through the creation of chimeric Hsp40 proteins by the replacement of the J-domain of a prokaryotic Hsp40 (DnaJ), we have tested the functional equivalence of J-domains from a number of divergent Hsp40s of mammalian and parasitic origin (malarial Pfj1 and Pfj4, trypanosomal Tcj3, human ERj3, ERj5, and Hsj1, and murine ERj1). An in vivo functional assay was used to test the functionality of the chimeric proteins on the basis of their ability to reverse the thermosensitivity of a dnaJ cbpA mutant Escherichia coli strain (OD259). The Hsp40 chimeras containing J-domains originating from soluble (cytosolic or endoplasmic reticulum (ER)-lumenal) Hsp40s were able to reverse the thermosensitivity of E. coli OD259. In all cases, modified derivatives of these chimeric proteins containing an His to Gln substitution in the HPD motif of the J-domain were unable to reverse the thermosensitivity of E. coli OD259. This suggested that these J-domains exerted their in vivo functionality through a specific interaction with E. coli Hsp70, DnaK. Interestingly, a Hsp40 chimera containing the J-domain of ERj1, an integral membrane-bound ER Hsp40, was unable to reverse the thermosensitivity of E. coli OD259, suggesting that this J-domain was unable to functionally interact with DnaK. Substitutions of conserved amino acid residues and motifs were made in all four helices (I-IV) and the loop regions of the J-domains, and the modified chimeric Hsp40s were tested for functionality using the in vivo assay. Substitution of a highly conserved basic residue in helix II of the J-domain was found to disrupt in vivo functionality for all the J-domains tested. We propose that helix II and the HPD motif of the J-domain represent the fundamental elements of a binding surface required for the interaction of Hsp40s with Hsp70s, and that this surface has been conserved in mammalian, parasitic and bacterial systems.
- Full Text:
- Date Issued: 2007
- Authors: Nicoll, W S , Botha, M , McNamara, Caryn , Schlange, M , Pesce, E R , Boshoff, Aileen , Ludewig, M H , Zimmerman, R , Cheetham, M E , Chapple, J P , Blatch, Gregory L
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6484 , http://hdl.handle.net/10962/d1006261 , http://www.sciencedirect.com/science/article/pii/S1357272506003268
- Description: Both prokaryotic and eukaryotic cells contain multiple heat shock protein 40 (Hsp40) and heat shock protein 70 (Hsp70) proteins, which cooperate as molecular chaperones to ensure fidelity at all stages of protein biogenesis. The Hsp40 signature domain, the J-domain, is required for binding of an Hsp40 to a partner Hsp70, and may also play a role in the specificity of the association. Through the creation of chimeric Hsp40 proteins by the replacement of the J-domain of a prokaryotic Hsp40 (DnaJ), we have tested the functional equivalence of J-domains from a number of divergent Hsp40s of mammalian and parasitic origin (malarial Pfj1 and Pfj4, trypanosomal Tcj3, human ERj3, ERj5, and Hsj1, and murine ERj1). An in vivo functional assay was used to test the functionality of the chimeric proteins on the basis of their ability to reverse the thermosensitivity of a dnaJ cbpA mutant Escherichia coli strain (OD259). The Hsp40 chimeras containing J-domains originating from soluble (cytosolic or endoplasmic reticulum (ER)-lumenal) Hsp40s were able to reverse the thermosensitivity of E. coli OD259. In all cases, modified derivatives of these chimeric proteins containing an His to Gln substitution in the HPD motif of the J-domain were unable to reverse the thermosensitivity of E. coli OD259. This suggested that these J-domains exerted their in vivo functionality through a specific interaction with E. coli Hsp70, DnaK. Interestingly, a Hsp40 chimera containing the J-domain of ERj1, an integral membrane-bound ER Hsp40, was unable to reverse the thermosensitivity of E. coli OD259, suggesting that this J-domain was unable to functionally interact with DnaK. Substitutions of conserved amino acid residues and motifs were made in all four helices (I-IV) and the loop regions of the J-domains, and the modified chimeric Hsp40s were tested for functionality using the in vivo assay. Substitution of a highly conserved basic residue in helix II of the J-domain was found to disrupt in vivo functionality for all the J-domains tested. We propose that helix II and the HPD motif of the J-domain represent the fundamental elements of a binding surface required for the interaction of Hsp40s with Hsp70s, and that this surface has been conserved in mammalian, parasitic and bacterial systems.
- Full Text:
- Date Issued: 2007
Molecular chaperones in biology, medicine and protein biotechnology
- Boshoff, Aileen, Nicoll, William S, Hennessy, Fritha, Ludewig, M H, Daniel, Sheril, Modisakeng, Keoagile W, Shonhai, Addmore, McNamara, Caryn, Bradley, Graeme, Blatch, Gregory L
- Authors: Boshoff, Aileen , Nicoll, William S , Hennessy, Fritha , Ludewig, M H , Daniel, Sheril , Modisakeng, Keoagile W , Shonhai, Addmore , McNamara, Caryn , Bradley, Graeme , Blatch, Gregory L
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6457 , http://hdl.handle.net/10962/d1004479
- Description: Molecular chaperones consist of several highly conserved families of proteins, many of which consist of heat shock proteins. The primary function of molecular chaperones is to facilitate the folding or refolding of proteins, and therefore they play an important role in diverse cellular processes including protein synthesis, protein translocation, and the refolding or degradation of proteins after cell stress. Cells are often exposed to different stressors, resulting in protein misfolding and aggregation. It is now well established that the levels of certain molecular chaperones are elevated during stress to provide protection to the cell. The focus of this review is on the impact of molecular chaperones in biology, medicine and protein biotechnology, and thus covers both fundamental and applied aspects of chaperone biology. Attention is paid to the functions and applications of molecular chaperones from bacterial and eukaryotic cells, focusing on the heat shock proteins 90 (Hsp90), 70 (Hsp70) and 40 (Hsp40) classes of chaperones, respectively. The role of these classes of chaperones in human diseases is discussed, as well as the parts played by chaperones produced by the causative agents of malaria and trypanosomiasis. Recent advances have seen the application of chaperones in improving the yields of a particular target protein in recombinant protein production. The prospects for the targeted use of molecular chaperones for the over-production of recombinant proteins is critically reviewed, and current research on these chaperones at Rhodes University is also discussed.
- Full Text:
- Date Issued: 2004
- Authors: Boshoff, Aileen , Nicoll, William S , Hennessy, Fritha , Ludewig, M H , Daniel, Sheril , Modisakeng, Keoagile W , Shonhai, Addmore , McNamara, Caryn , Bradley, Graeme , Blatch, Gregory L
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6457 , http://hdl.handle.net/10962/d1004479
- Description: Molecular chaperones consist of several highly conserved families of proteins, many of which consist of heat shock proteins. The primary function of molecular chaperones is to facilitate the folding or refolding of proteins, and therefore they play an important role in diverse cellular processes including protein synthesis, protein translocation, and the refolding or degradation of proteins after cell stress. Cells are often exposed to different stressors, resulting in protein misfolding and aggregation. It is now well established that the levels of certain molecular chaperones are elevated during stress to provide protection to the cell. The focus of this review is on the impact of molecular chaperones in biology, medicine and protein biotechnology, and thus covers both fundamental and applied aspects of chaperone biology. Attention is paid to the functions and applications of molecular chaperones from bacterial and eukaryotic cells, focusing on the heat shock proteins 90 (Hsp90), 70 (Hsp70) and 40 (Hsp40) classes of chaperones, respectively. The role of these classes of chaperones in human diseases is discussed, as well as the parts played by chaperones produced by the causative agents of malaria and trypanosomiasis. Recent advances have seen the application of chaperones in improving the yields of a particular target protein in recombinant protein production. The prospects for the targeted use of molecular chaperones for the over-production of recombinant proteins is critically reviewed, and current research on these chaperones at Rhodes University is also discussed.
- Full Text:
- Date Issued: 2004
The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x
- Daniyan, Michael O, Boshoff, Aileen, Prinsloo, Earl, Pesce, Eva-Rachele, Blatch, Gregory L
- Authors: Daniyan, Michael O , Boshoff, Aileen , Prinsloo, Earl , Pesce, Eva-Rachele , Blatch, Gregory L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66098 , vital:28901 , https://doi.org/10.1371/journal.pone.0148517
- Description: publisher version , Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentration-dependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria. , This work was supported by grants from the National Research Foundation (NRF) and Medical Research Council (MRC) of South Africa. The ProteOn XPR36 IAS was purchased from a National Nanotechnology Equipment Programme grant from the Department of Science and Technology and the NRF of South Africa. Michael O. Daniyan was a recipient of the Education Trust Fund (ETF) Academic Staff Training and Development (AST and D) scholarship of Obafemi Awolowo University, Ile-Ife, Nigeria and a Rhodes University Council research bursary
- Full Text:
- Date Issued: 2016
- Authors: Daniyan, Michael O , Boshoff, Aileen , Prinsloo, Earl , Pesce, Eva-Rachele , Blatch, Gregory L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66098 , vital:28901 , https://doi.org/10.1371/journal.pone.0148517
- Description: publisher version , Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentration-dependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria. , This work was supported by grants from the National Research Foundation (NRF) and Medical Research Council (MRC) of South Africa. The ProteOn XPR36 IAS was purchased from a National Nanotechnology Equipment Programme grant from the Department of Science and Technology and the NRF of South Africa. Michael O. Daniyan was a recipient of the Education Trust Fund (ETF) Academic Staff Training and Development (AST and D) scholarship of Obafemi Awolowo University, Ile-Ife, Nigeria and a Rhodes University Council research bursary
- Full Text:
- Date Issued: 2016
Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3
- Nyakundi, David O, Vuko, Loyiso A M, Bentley, Stephen J, Hoppe, Heinrich C, Blatch, Gregory L, Boshoff, Aileen
- Authors: Nyakundi, David O , Vuko, Loyiso A M , Bentley, Stephen J , Hoppe, Heinrich C , Blatch, Gregory L , Boshoff, Aileen
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66109 , vital:28903 , https://doi.org/10.1371/journal.pone.0156446
- Description: publisher version , The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria. , This work was funded by grants from the National Research Foundation (NRF); grant number 87663 and Deutsche Forschungsgemeinschaft (DFG); grant number LI 402/14-1. D.O.N. is the recipient of academic development and training funds from Mwenge Catholic University, Moshi, Tanzania. S.J.B. is the recipient of an NRF Doctoral Innovation Scholarship.
- Full Text:
- Date Issued: 2016
- Authors: Nyakundi, David O , Vuko, Loyiso A M , Bentley, Stephen J , Hoppe, Heinrich C , Blatch, Gregory L , Boshoff, Aileen
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66109 , vital:28903 , https://doi.org/10.1371/journal.pone.0156446
- Description: publisher version , The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria. , This work was funded by grants from the National Research Foundation (NRF); grant number 87663 and Deutsche Forschungsgemeinschaft (DFG); grant number LI 402/14-1. D.O.N. is the recipient of academic development and training funds from Mwenge Catholic University, Moshi, Tanzania. S.J.B. is the recipient of an NRF Doctoral Innovation Scholarship.
- Full Text:
- Date Issued: 2016
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