Molecular Chaperones Involved in Protein Recovery from Aggregates are Present in Protozoa Causative of Malaria and Leishmaniasis

Author(s): Fernanda A.H. Batista, Paulo R. Dores-Silva, Júlio C. Borges*

Journal Name: Current Proteomics

Volume 16 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Molecular chaperones have several critical functions in protein metabolism. Among them, some are involved in processes that culminate in the extraction of entangled polypeptides from protein aggregates, releasing unfolded structures prone to be refolded or directed to degradation. This action avoids the effect of toxic aggregates on cells and tissues. Molecular chaperones belonging to the Hsp100 family are widely distributed from unicellular and sessile organisms up to fungi and plants, exerting key functions related to the reduction of the effects caused by different forms of stress. The Hsp100 proteins belong to the AAA+ (ATPases Associated with diverse cellular Activities) family and form multichaperone systems with Hsp70 and small Hsp chaperones families. However, Hsp100 are absent in metazoan, where protein disaggregation action is performed by a system involving the Hsp70 family, including Hsp110 and J-protein co-chaperones. Here, the structural and functional aspects of these protein disaggregation systems will be reviewed and discussed in the perspective of the Hsp100 system absent in the metazoan kingdom. This feature focuses on Hsp100 as a hot spot for drug discovery against human infectious diseases such as leishmaniasis and malaria, as Hsp100 is critical for microorganisms. The current data available for Hsp100 in Leishmania spp. and Plasmodium spp. are also reviewed.

Keywords: Hsp100, Hsp110, Hsp70, J-proteins, protein aggregation, protein disaggregation.

Dobson, C.M. Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol., 2004, 15(1), 3-16.
Zolkiewski, M.; Zhang, T.; Nagy, M. Aggregate reactivation mediated by the Hsp100 chaperones. Arch. Biochem. Biophys., 2012, 520(1), 1-6.
Scior, A.; Juenemann, K.; Kirstein, J. Cellular strategies to cope with protein aggregation. Essays Biochem., 2016, 60(2), 153-161.
Batista, F.A.; Gava, L.M.; Pinheiro, G.M.; Ramos, C.H.; Borges, J.C. From conformation to interaction: Techniques to explore the Hsp70/Hsp90 Network. Curr. Protein Pept. Sci., 2015, 16(8), 735-753.
Borges, J.C.; Ramos, C.H. Protein folding assisted by chaperones. Protein Pept. Lett., 2005, 12(3), 257-261.
Jaenicke, R.; Seckler, R. Seckler, R. Spontaneous versus assisted protein folding. In In: Molecular Chaperones and Folding Catalysts Regulation, Cellular Function and Mechanism,; Bukau, B., Ed. Amsterdam: Harwood Academic Publishers,. , 1999.
Jaenicke, R. Folding and association of proteins. Prog. Biophys. Mol. Biol., 1987, 49(2-3), 117-237.
Mogk, A.; Haslberger, T.; Tessarz, P.; Bukau, B. Common and specific mechanisms of AAA+ proteins involved in protein quality control. Biochem. Soc. Trans., 2008, 36(Pt 1), 120-125.
Saibil, H. Chaperone machines for protein folding, unfolding and disaggregation. Nat. Rev. Mol. Cell Biol., 2013, 14(10), 630-642.
Hartl, F.U.; Hayer-Hartl, M. Protein folding - molecular chaperones in the cytosol: From nascent chain to folded protein. Science, 2002, 295(5561), 1852-1858.
Mokry, D.Z.; Abrahão, J.; Ramos, C.H. Disaggregases, molecular chaperones that resolubilize protein aggregates. An. Acad. Bras. Cienc., 2015, 87(2)(Suppl.), 1273-1292.
Shorter, J. The mammalian disaggregase machinery: Hsp110 synergizes with Hsp70 and Hsp40 to catalyze protein disaggregation and reactivation in a cell-free system. PLoS One, 2011, 6(10), e26319.
Nillegoda, N.B.; Kirstein, J.; Szlachcic, A.; Berynskyy, M.; Stank, A.; Stengel, F.; Arnsburg, K.; Gao, X.; Scior, A.; Aebersold, R.; Guilbride, D.L.; Wade, R.C.; Morimoto, R.I.; Mayer, M.P.; Bukau, B. Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation. Nature, 2015, 524(7564), 247-251.
Mogk, A.; Kummer, E.; Bukau, B. Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation. Front. Mol. Biosci., 2015, 2, 22.
Rampelt, H.; Kirstein-Miles, J.; Nillegoda, N.B.; Chi, K.; Scholz, S.R.; Morimoto, R.I.; Bukau, B. Metazoan Hsp70 machines use Hsp110 to power protein disaggregation. EMBO J., 2012, 31(21), 4221-4235.
Żwirowski, S.; Kłosowska, A.; Obuchowski, I.; Nillegoda, N.B.; Piróg, A.; Ziętkiewicz, S.; Bukau, B.; Mogk, A.; Liberek, K. Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding. EMBO J., 2017, 36(6), 783-796.
Schaupp, A.; Marcinowski, M.; Grimminger, V.; Bösl, B.; Walter, S. Processing of proteins by the molecular chaperone Hsp104. J. Mol. Biol., 2007, 370(4), 674-686.
Schirmer, E.C.; Glover, J.R.; Singer, M.A.; Lindquist, S. HSP100/Clp proteins: A common mechanism explains diverse functions. Trends Biochem. Sci., 1996, 21(8), 289-296.
Shorter, J. Engineering therapeutic protein disaggregases. Mol. Biol. Cell, 2016, 27(10), 1556-1560.
Sweeny, E.A.; Shorter, J. Mechanistic and structural insights into the prion-disaggregase activity of Hsp104. J. Mol. Biol., 2016, 428(9 Pt B), 1870-1885.
de Marco, A.; Deuerling, E.; Mogk, A.; Tomoyasu, T.; Bukau, B. Chaperone-based procedure to increase yields of soluble recombinant proteins produced in E. coli. BMC Biotechnol., 2007, 7(1), 32.
Haslberger, T.; Bukau, B.; Mogk, A. Towards a unifying mechanism for ClpB/Hsp104-mediated protein disaggregation and prion propagation. Biochem. Cell Biol., 2010, 88(1), 63-75.
Lipińska, N.; Ziętkiewicz, S.; Sobczak, A.; Jurczyk, A.; Potocki, W.; Morawiec, E.; Wawrzycka, A.; Gumowski, K.; Ślusarz, M.; Rodziewicz-Motowidło, S.; Chruściel, E.; Liberek, K. Disruption of ionic interactions between the Nucleotide Binding Domain 1 (NBD1) and Middle (M) domain in Hsp100 disaggregase unleashes toxic hyperactivity and partial independence from Hsp70. J. Biol. Chem., 2013, 288(4), 2857-2869.
Lee, S.; Sowa, M.E.; Watanabe, Y.H.; Sigler, P.B.; Chiu, W.; Yoshida, M.; Tsai, F.T. The structure of ClpB: A molecular chaperone that rescues proteins from an aggregated state. Cell, 2003, 115(2), 229-240.
Hanson, P.I.; Whiteheart, S.W. AAA+ proteins: Have engine, will work. Nat. Rev. Mol. Cell Biol., 2005, 6(7), 519-529.
Kitagawa, M.; Wada, C.; Yoshioka, S.; Yura, T. Expression of ClpB, an analog of the ATP-dependent protease regulatory subunit in Escherichia coli, is controlled by a heat shock sigma factor (sigma 32). J. Bacteriol., 1991, 173(14), 4247-4253.
Woo, K.M.; Kim, K.I.; Goldberg, A.L.; Ha, D.B.; Chung, C.H. The heat-shock protein ClpB in Escherichia coli is a protein-activated ATPase. J. Biol. Chem., 1992, 267(28), 20429-20434.
Squires, C.L.; Pedersen, S.; Ross, B.M.; Squires, C. ClpB is the Escherichia coli heat shock protein F84.1. J. Bacteriol., 1991, 173(14), 4254-4262.
Sanchez, Y.; Lindquist, S.L. HSP104 required for induced thermotolerance. Science, 1990, 248(4959), 1112-1115.
Parsell, D.A.; Sanchez, Y.; Stitzel, J.D.; Lindquist, S. Hsp104 is a highly conserved protein with two essential nucleotide-binding sites. Nature, 1991, 353(6341), 270-273.
Lee, Y.R.; Nagao, R.T.; Key, J.L. A soybean 101-kD heat shock protein complements a yeast HSP104 deletion mutant in acquiring thermotolerance. Plant Cell, 1994, 6(12), 1889-1897.
Singh, A.; Singh, U.; Mittal, D.; Grover, A. Genome-wide analysis of rice ClpB/HSP100, ClpC and ClpD genes. BMC Genom., 2010, 11, 95.
Cagliari, T.C.; da Silva, V.C.; Borges, J.C.; Prando, A.; Tasic, L.; Ramos, C.H. Sugarcane Hsp101 is a hexameric chaperone that binds nucleotides. Int. J. Biol. Macromol., 2011, 49(5), 1022-1030.
Zolkiewski, M.; Kessel, M.; Ginsburg, A.; Maurizi, M.R. Nucleotide-dependent oligomerization of ClpB from Escherichia coli. Protein Sci., 1999, 8(9), 1899-1903.
Lin, J.; Lucius, A.L. Examination of the dynamic assembly equilibrium for E. coli ClpB. Proteins, 2015, 83(11), 2008-2024.
Parsell, D.A.; Kowal, A.S.; Lindquist, S. Saccharomyces cerevisiae Hsp104 protein. Purification and characterization of ATP-induced structural changes. J. Biol. Chem., 1994, 269(6), 4480-4487.
Aguado, A.; Fernández-Higuero, J.A.; Moro, F.; Muga, A. Chaperone-assisted protein aggregate reactivation: Different solutions for the same problem. Arch. Biochem. Biophys., 2015, 580, 121-134.
Rosenzweig, R.; Farber, P.; Velyvis, A.; Rennella, E.; Latham, M.P.; Kay, L.E.; Clp, B. N-terminal domain plays a regulatory role in protein disaggregation. Proc. Natl. Acad. Sci. USA, 2015, 112(50), E6872-E6881.
Lee, J.; Kim, J.H.; Biter, A.B.; Sielaff, B.; Lee, S.; Tsai, F.T. Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor. Proc. Natl. Acad. Sci. USA, 2013, 110(21), 8513-8518.
Glover, J.R.; Lindquist, S. Hsp104, Hsp70, and Hsp40: A novel chaperone system that rescues previously aggregated proteins. Cell, 1998, 94(1), 73-82.
Mogk, A.; Tomoyasu, T.; Goloubinoff, P.; Rüdiger, S.; Röder, D.; Langen, H.; Bukau, B. Identification of thermolabile Escherichia coli proteins: Prevention and reversion of aggregation by DnaK and ClpB. EMBO J., 1999, 18(24), 6934-6949.
Goloubinoff, P.; Mogk, A.; Zvi, A.P.; Tomoyasu, T.; Bukau, B. Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network. Proc. Natl. Acad. Sci. USA, 1999, 96(24), 13732-13737.
Reidy, M.; Miot, M.; Masison, D.C. Prokaryotic chaperones support yeast prions and thermotolerance and define disaggregation machinery interactions. Genetics, 2012, 192(1), 185-193.
Yuan, A.H.; Garrity, S.J.; Nako, E.; Hochschild, A. Prion propagation can occur in a prokaryote and requires the ClpB chaperone. eLife, 2014, 3, e02949.
Mishra, R.C.; Grover, A. ClpB/Hsp100 proteins and heat stress tolerance in plants. Crit. Rev. Biotech., 2015, 1549-7801.
Hodson, S.; Marshall, J.J.; Burston, S.G. Mapping the road to recovery: The ClpB/Hsp104 molecular chaperone. J. Struct. Biol., 2012, 179(2), 161-171.
Chernova, T.A.; Wilkinson, K.D.; Chernoff, Y.O. Prions, chaperones, and proteostasis in yeast. Cold Spring Harb. Perspect. Biol., 2017, 9(2)
Singh, A.; Grover, A. Plant Hsp100/ClpB-like proteins: Poorly-analyzed cousins of yeast ClpB machine. Plant Mol. Biol., 2010, 74(4-5), 395-404.
Seraphim, T.V.; Ramos, C.H.I.; Borges, J.C. The interaction networks of Hsp70 and Hsp90 in the Plasmodium and Leishmania parasites.In The molecular chaperones interaction networks in protein folding and degradation; Houry, W., Ed.; Springer: New York, 2014, Vol. 1, pp. 445-481.
Krobitsch, S.; Clos, J. A novel role for 100 kD heat shock proteins in the parasite Leishmania donovani. Cell Stress Chaperones, 1999, 4(3), 191-198.
McCall, L.I.; Matlashewski, G. Involvement of the Leishmania donovani virulence factor A2 in protection against heat and oxidative stress. Exp. Parasitol., 2012, 132(2), 109-115.
Brandau, S.; Dresel, A.; Clos, J. High constitutive levels of heat-shock proteins in human-pathogenic parasites of the genus Leishmania. Biochem. J., 1995, 310(Pt 1), 225-232.
Hubel, A.; Brandau, S.; Dresel, A.; Clos, J. A member of the Clpb family of stress proteins is expressed during heat-shock in Leishmania Spp. Mol. Biochem. Parasitol., 1995, 70(1-2), 107-118.
Krobitsch, S.; Brandau, S.; Hoyer, C.; Schmetz, C.; Hübel, A.; Clos, J. Leishmania donovani heat shock protein 100. Characterization and function in amastigote stage differentiation. J. Biol. Chem., 1998, 273(11), 6488-6494.
Larreta, R.; Soto, M.; Quijada, L.; Folgueira, C.; Abanades, D.R.; Alonso, C.; Requena, J.M. The expression of HSP83 genes in Leishmania infantum is affected by temperature and by stage-differentiation and is regulated at the levels of mRNA stability and translation. BMC Mol. Biol., 2004, 5, 3.
Clos, J.; Klaholz, L.; Kroemer, M.; Krobitsch, S.; Lindquist, S. Heat shock protein 100 and the amastigote stage-specific A2 proteins of Leishmania donovani. Med. Microbiol. Immunol., 2001, 190(1-2), 47-50.
Clos, J.; Krobitsch, S. Heat shock as a regular feature of the life cycle of Leishmania parasites. Am. Zool., 1999, 39(6), 848-856.
Hübel, A.; Krobitsch, S.; Hörauf, A.; Clos, J. Leishmania major Hsp100 is required chiefly in the mammalian stage of the parasite. Mol. Cell. Biol., 1997, 17(10), 5987-5995.
Lassmann, T.; Sonnhammer, E.L. Kalign--an accurate and fast multiple sequence alignment algorithm. BMC Bioinfo., 2005, 6, 298.
WHO; World Malaria Report 2016;, World Health Organization: Geneva, 2016, 2017; pp. 186.. 2016.
Hakamada, K.; Watanabe, H.; Kawano, R.; Noguchi, K.; Yohda, M. Expression and characterization of the Plasmodium translocon of the exported proteins component EXP2. Biochem. Biophys. Res. Commun., 2017, 482(4), 700-705.
Deponte, M.; Hoppe, H.C.; Lee, M.C.; Maier, A.G.; Richard, D.; Rug, M.; Spielmann, T.; Przyborski, J.M. Wherever I may roam: Protein and membrane trafficking in P. falciparum-infected red blood cells. Mol. Biochem. Parasitol., 2012, 186(2), 95-116.
AhYoung. A.P.; Koehl, A.; Cascio, D.; Egea, P.F. Structural mapping of the ClpB ATPases of Plasmodium falciparum: Targeting protein folding and secretion for antimalarial drug design. Protein Sci., 2015, 24(9), 1508-1520.
Rhiel, M.; Bittl, V.; Tribensky, A.; Charnaud, S.C.; Strecker, M.; Müller, S.; Lanzer, M.; Sanchez, C.; Schaeffer-Reiss, C.; Westermann, B.; Crabb, B.S.; Gilson, P.R.; Külzer, S.; Przyborski, J.M. Trafficking of the exported P. falciparum chaperone PfHsp70x. Sci. Rep., 2016, 6, 36174.
Charpian, S.; Przyborski, J.M. Protein transport across the parasitophorous vacuole of Plasmodium falciparum: Into the great wide open. Traffic, 2008, 9(2), 157-165.
de Koning-Ward, T.F.; Gilson, P.R.; Boddey, J.A.; Rug, M.; Smith, B.J.; Papenfuss, A.T.; Sanders, P.R.; Lundie, R.J.; Maier, A.G.; Cowman, A.F.; Crabb, B.S. A newly discovered protein export machine in malaria parasites. Nature, 2009, 459(7249), 945-949.
Peng, M.; Cascio, D.; Egea, P.F. Crystal structure and solution characterization of the thioredoxin-2 from Plasmodium falciparum, a constituent of an essential parasitic protein export complex. Biochem. Biophys. Res. Commun., 2015, 456(1), 403-409.
Elsworth, B.; Matthews, K.; Nie, C.Q.; Kalanon, M.; Charnaud, S.C.; Sanders, P.R.; Chisholm, S.A.; Counihan, N.A.; Shaw, P.J.; Pino, P.; Chan, J.A.; Azevedo, M.F.; Rogerson, S.J.; Beeson, J.G.; Crabb, B.S.; Gilson, P.R.; de Koning-Ward, T.F. PTEX is an essential nexus for protein export in malaria parasites. Nature, 2014, 511(7511), 587-591.
El Bakkouri, M.; Pow, A.; Mulichak, A.; Cheung, K.L.; Artz, J.D.; Amani, M.; Fell, S.; de Koning-Ward, T.F.; Goodman, C.D.; McFadden, G.I.; Ortega, J.; Hui, R.; Houry, W.A. The Clp chaperones and proteases of the human malaria parasite Plasmodium falciparum. J. Mol. Biol., 2010, 404(3), 456-477.
Pavithra, S.R.; Kumar, R.; Tatu, U. Systems analysis of chaperone networks in the malarial parasite Plasmodium falciparum. PLOS Comput. Biol., 2007, 3(9), 1701-1715.
Beck, J.R.; Muralidharan, V.; Oksman, A.; Goldberg, D.E. HSP101/PTEX mediates export of diverse malaria effector proteins into the host erythrocyte. Nature, 2014, 511(7511), 592-595.
Pesce, E.R.; Blatch, G.L. Plasmodial Hsp40 and Hsp70 chaperones: Current and future perspectives. Parasitology, 2014, 141(9), 1167-1176.
Przyborski, J.M.; Diehl, M.; Blatch, G.L. Plasmodial HSP70s are functionally adapted to the malaria parasite life cycle. Front. Mol. Biosci., 2015, 2(34), 34.
Nillegoda, N.B.; Bukau, B. Metazoan Hsp70-based protein disaggregases: Emergence and mechanisms. Front. Mol. Biosci., 2015, 2, 57.
Karlin, S.; Brocchieri, L. Heat shock protein 70 family: Multiple sequence comparisons, function, and evolution. J. Mol. Evol., 1998, 47(5), 565-577.
da Silva, K.P.; Borges, J.C. The molecular chaperone Hsp70 family members function by a bidirectional heterotrophic allosteric mechanism. Protein Pept. Lett., 2011, 18(2), 132-142.
Daugaard, M.; Rohde, M.; Jaattela, M. The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett., 2007, 581(19), 3702-3710.
Mayer, M.P.; Schröder, H.; Rüdiger, S.; Paal, K.; Laufen, T.; Bukau, B. Multistep mechanism of substrate binding determines chaperone activity of Hsp70. Nat. Struct. Biol., 2000, 7(7), 586-593.
Mayer, M.P.; Brehmer, D.; Gässler, C.S.; Bukau, B. Hsp70 chaperone machines. Adv. Protein Chem., 2001, 59, 1-44.
Young, J.C. Mechanisms of the Hsp70 chaperone system. Biochem. Cell Biol., 2010, 88(2), 291-300.
Mayer, M.P.; Bukau, B. Hsp70 chaperones: Cellular functions and molecular mechanism. Cell. Mol. Life Sci., 2005, 62(6), 670-684.
Wegele, H.; Müller, L.; Buchner, J. Hsp70 and Hsp90--a relay team for protein folding. Rev. Physiol. Biochem. Pharmacol., 2004, 151, 1-44.
Takayama, S.; Reed, J.C. Molecular chaperone targeting and regulation by BAG family proteins. Nat. Cell Biol., 2001, 3(10), E237-E241.
Kabani, M.; McLellan, C.; Raynes, D.A.; Guerriero, V.; Brodsky, J.L. HspBP1, a homologue of the yeast Fes1 and Sls1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Lett., 2002, 531(2), 339-342.
Shaner, L.; Sousa, R.; Morano, K.A. Characterization of Hsp70 binding and nucleotide exchange by the yeast Hsp110 chaperone Sse1. Biochemistry, 2006, 45(50), 15075-15084.
Raviol, H.; Sadlish, H.; Rodriguez, F.; Mayer, M.P.; Bukau, B. Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide exchange factor. EMBO J., 2006, 25(11), 2510-2518.
Goeckeler, J.L.; Stephens, A.; Lee, P.; Caplan, A.J.; Brodsky, J.L. Overexpression of yeast Hsp110 homolog Sse1p suppresses ydj1-151 thermosensitivity and restores Hsp90-dependent activity. Mol. Biol. Cell, 2002, 13(8), 2760-2770.
Easton, D.P.; Kaneko, Y.; Subjeck, J.R. The hsp110 and Grp1 70 stress proteins: Newly recognized relatives of the Hsp70s. Cell Stress Chaperones, 2000, 5(4), 276-290.
Andréasson, C.; Fiaux, J.; Rampelt, H.; Druffel-Augustin, S.; Bukau, B. Insights into the structural dynamics of the Hsp110-Hsp70 interaction reveal the mechanism for nucleotide exchange activity. Proc. Natl. Acad. Sci. USA, 2008, 105(43), 16519-16524.
Schuermann, J.P.; Jiang, J.; Cuellar, J.; Llorca, O.; Wang, L.; Gimenez, L.E.; Jin, S.; Taylor, A.B.; Demeler, B.; Morano, K.A.; Hart, P.J.; Valpuesta, J.M.; Lafer, E.M.; Sousa, R. Structure of the Hsp110: Hsc70 nucleotide exchange machine. Mol. Cell, 2008, 31(2), 232-243.
Kampinga, H.H.; Craig, E.A. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat. Rev. Mol. Cell Biol., 2010, 11(8), 579-592.
Cyr, D.M.; Ramos, C.H. Specification of Hsp70 function by type I and Type II Hsp40. In The Networking of Chaperones by Cochaperones,, Blatch, G.L.; Edkins, A.L., Eds. Springer International Publishing: 2015, 78, pp. 91-102.
Mattoo, R.U.; Sharma, S.K.; Priya, S.; Finka, A.; Goloubinoff, P. Hsp110 is a bona fide chaperone using ATP to unfold stable misfolded polypeptides and reciprocally collaborate with Hsp70 to solubilize protein aggregates. J. Biol. Chem., 2013, 288(29), 21399-213411.
Requena, J.M.; Montalvo, A.M.; Fraga, J. Molecular chaperones of Leishmania: Central players in many stress-related and -unrelated physiological processes. BioMed Res. Int., 2015, 2015, 301326.
Zininga, T.; Achilonu, I.; Hoppe, H.; Prinsloo, E.; Dirr, H.W.; Shonhai, A. Overexpression, purification and characterisation of the Plasmodium falciparum Hsp70-z (PfHsp70-z) protein. PLoS One, 2015, 10(6), e0129445.
Zininga, T.; Achilonu, I.; Hoppe, H.; Prinsloo, E.; Dirr, H.W.; Shonhai, A. Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion. Cell Stress Chaperones, 2016, 21(3), 499-513.
Shonhai, A.; Maier, A.G.; Przyborski, J.M.; Blatch, G.L. Intracellular protozoan parasites of humans: The role of molecular chaperones in development and pathogenesis. Protein Pept. Lett., 2011, 18(2), 143-157.
Njunge, J.M.; Ludewig, M.H.; Boshoff, A.; Pesce, E.R.; Blatch, G.L. Hsp70s and J proteins of Plasmodium parasites infecting rodents and primates: Structure, function, clinical relevance, and drug targets. Curr. Pharm. Des., 2013, 19(3), 387-403.
Zininga, T.; Pooe, O.J.; Makhado, P.B.; Ramatsui, L.; Prinsloo, E.; Achilonu, I.; Dirr, H.; Shonhai, A. Polymyxin B inhibits the chaperone activity of Plasmodium falciparum Hsp70. Cell Stress Chaperones, 2017, 22(5), 707-715.
Shonhai, A.; Botha, M.; de Beer, T.A.P.; Boshoff, A.; Blatch, G.L. Structure-function study of a Plasmodium falciparum Hsp70 using three dimensional modelling and in vitro analyses. Protein Pept. Lett., 2008, 15, 1117-1125.
Muralidharan, V.; Oksman, A.; Pal, P.; Lindquist, S.; Goldberg, D.E. Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers. Nat. Commun., 2012, 3, 1310.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [12 - 21]
Pages: 10
DOI: 10.2174/1570164615666180626123823
Price: $25

Article Metrics

PDF: 25