Skip to main content

Co-chaperones of Hsp90 in Plasmodium falciparum and their concerted roles in cellular regulation

  • CHUN-SONG CHUA (a1), HUIYU LOW (a1) and TIOW-SUAN SIM (a1)

Co-chaperones are well-known regulators of heat shock protein 90 (Hsp90). Hsp90 is a molecular chaperone that is essential in the eukaryotes for the folding and activation of numerous proteins involved in important cellular processes such as signal transduction, growth and developmental regulation. Co-chaperones assist Hsp90 in the protein folding process by modulating conformational changes to promote client protein interaction and functional maturation. With the recognition of Plasmodium falciparum Hsp90 (PfHsp90) as a potential antimalarial drug target, there is obvious interest in the study of its co-chaperones in their partnership in regulating cellular processes in malaria parasite. Previous studies on PfHsp90 have identified more than 10 co-chaperones in P. falciparum genome. However, many of them remained annotated as putative proteins as their functionality has not been validated experimentally. So far, only five co-chaperones, PfHop, Pfp23, PfAha1, PfPP5 and PfFKBP35 have been characterized and shown to interact with PfHsp90. This review will summarize current knowledge on the co-chaperones in P. falciparum and discuss their regulatory roles on PfHsp90. As certain eukaryotic co-chaperones have also been implicated in altering the affinity of Hsp90 for its inhibitor, this review will also examine plasmodial co-chaperones’ potential influence on approaches towards designing antimalarials targeting PfHsp90.

Corresponding author
* Corresponding author: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore. E-mail:
Hide All
Acharya, P., Kumar, R. and Tatu, U. (2007). Chaperoning a cellular upheaval in malaria: heat shock proteins in Plasmodium falciparum . Molecular and Biochemical Parasitology 153, 8594.
Alag, R., Bharatham, N., Dong, A., Hills, T., Harikishore, A., Widjaja, A. A., Shochat, S. G., Hui, R. and Yoon, H. S. (2009). Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide. Protein Science 18, 21152124.
Angel, S. O., Matrajt, M. and Echeverria, P. C. (2012). A review of recent patents on the protozoan parasite HSP90 as a drug target. Recent Patents on Biotechnology 7, 28.
Ballinger, C. A., Connell, P., Wu, Y., Hu, Z., Thompson, L. J., Yin, L. Y. and Patterson, C. (1999). Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Molecular and Cellular Biology 19, 45354545.
Bandhakavi, S., McCann, R. O., Hanna, D. E. and Glover, C. V. (2003). A positive feedback loop between protein kinase CKII and Cdc37 promotes the activity of multiple protein kinases. Journal of Biological Chemistry 278, 28292836.
Banumathy, G., Singh, V., Pavithra, S. R. and Tatu, U. (2003). Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. Journal of Biological Chemistry 278, 1833618345.
Barent, R. L., Nair, S. C., Carr, D. C., Ruan, Y., Rimerman, R. A., Fulton, J., Zhang, Y. and Smith, D. F. (1998). Analysis of FKBP51/FKBP52 chimeras and mutants for Hsp90 binding and association with progesterone receptor complexes. Molecular Endocrinology 12, 342354.
Barik, S. (2006). Immunophilins: for the love of proteins. Cellular and Molecular Life Sciences 63, 28892900.
Basso, A. D., Solit, D. B., Chiosis, G., Giri, B., Tsichlis, P. and Rosen, N. (2002). Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. Journal of Biological Chemistry 277, 3985839866.
Bell, A., Wernli, B. and Franklin, R. M. (1994). Roles of peptidyl-prolyl cis-trans isomerase and calcineurin in the mechanisms of antimalarial action of cyclosporin A, FK506, and rapamycin. Biochemical Pharmacology 48, 495503.
Bharatham, N., Chang, M. W. and Yoon, H. S. (2011). Targeting FK506 binding proteins to fight malarial and bacterial infections: current advances and future perspectives. Current Medicinal Chemistry 18, 18741889.
Caplan, A. J., Mandal, A. K. and Theodoraki, M. A. (2007). Molecular chaperones and protein kinase quality control. Trends in Cell Biology 17, 8792.
Chen, M. S., Silverstein, A. M., Pratt, W. B. and Chinkers, M. (1996). The tetratricopeptide repeat domain of protein phosphatase 5 mediates binding to glucocorticoid receptor heterocomplexes and acts as a dominant negative mutant. Journal of Biological Chemistry 271, 3231532320.
Chen, S. and Smith, D. F. (1998). Hop as an adaptor in the heat shock protein 70 (Hsp70) and hsp90 chaperone machinery. Journal of Biological Chemistry 273, 3519435200.
Chua, C. S., Low, H., Goo, K. S. and Sim, T. S. (2010). Characterization of Plasmodium falciparum co-chaperone p23: its intrinsic chaperone activity and interaction with Hsp90. Cellular and Molecular Life Sciences 67, 16751686.
Chua, C. S., Low, H., Lehming, N. and Sim, T. S. (2012). Molecular analysis of Plasmodium falciparum co-chaperone Aha1 supports its interaction with and regulation of Hsp90 in the malaria parasite. International Journal of Biochemistry and Cell Biology 44, 233245.
Connell, P., Ballinger, C. A., Jiang, J., Wu, Y., Thompson, L. J., Hohfeld, J. and Patterson, C. (2001). The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nature Cell Biology 3, 9396.
D'Andrea, L. D. and Regan, L. (2003). TPR proteins: the versatile helix. Trends in Biochemical Sciences 28, 655662.
Dickey, C. A., Kamal, A., Lundgren, K., Klosak, N., Bailey, R. M., Dunmore, J., Ash, P., Shoraka, S., Zlatkovic, J., Eckman, C. B., Patterson, C., Dickson, D. W., Nahman, N. S. Jr., Hutton, M., Burrows, F. and Petrucelli, L. (2007). The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. Journal of Clinical Investigation 117, 648658.
Dittmar, K. D., Hutchison, K. A., Owens-Grillo, J. K. and Pratt, W. B. (1996). Reconstitution of the steroid receptor. hsp90 heterocomplex assembly system of rabbit reticulocyte lysate. Journal of Biological Chemistry 271, 1283312839.
Dobson, S., Kar, B., Kumar, R., Adams, B. and Barik, S. (2001). A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum . BMC Microbiology 1, 31.
Dolinski, K. J., Cardenas, M. E. and Heitman, J. (1998). CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses cyclophilin 40 mutations and interacts with Hsp90. Molecular and Cellular Biology 18, 73447352.
Duina, A. A., Marsh, J. A. and Gaber, R. F. (1996). Identification of two CyP-40-like cyclophilins in Saccharomyces cerevisiae, one of which is required for normal growth. Yeast 12, 943952.
Eckert, K., Saliou, J. M., Monlezun, L., Vigouroux, A., Atmane, N., Caillat, C., Quevillon-Cheruel, S., Madiona, K., Nicaise, M., Lazereg, S., Van Dorsselaer, A., Sanglier-Cianferani, S., Meyer, P. and Morera, S. (2010). The Pih1-Tah1 cochaperone complex inhibits Hsp90 molecular chaperone ATPase activity. Journal of Biological Chemistry 285, 3130431312.
Famin, O. and Ginsburg, H. (2003). The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase. Parasite 10, 3950.
Fang, Y., Fliss, A. E., Rao, J. and Caplan, A. J. (1998). SBA1 encodes a yeast hsp90 cochaperone that is homologous to vertebrate p23 proteins. Molecular and Cellular Biology 18, 37273734.
Fanghanel, J. and Fischer, G. (2004). Insights into the catalytic mechanism of peptidyl prolyl cis/trans isomerases. Frontiers in Bioscience 9, 34533478.
Fletcher, S. and Hamilton, A. D. (2006). Targeting protein-protein interactions by rational design: mimicry of protein surfaces. Journal of the Royal Society, Interface 3, 215233.
Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C. and Picard, D. (2008). p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity. Molecular and Cellular Biology 28, 34463456.
Gaiser, A. M., Kretzschmar, A. and Richter, K. (2010). Cdc37-Hsp90 complexes are responsive to nucleotide-induced conformational changes and binding of further cofactors. Journal of Biological Chemistry 285, 4092140932.
Giaever, G., Chu, A. M., Ni, L., Connelly, C., Riles, L., Veronneau, S., Dow, S., Lucau-Danila, A., Anderson, K., Andre, B., Arkin, A. P., Astromoff, A., El-Bakkoury, M., Bangham, R., Benito, R., Brachat, S., Campanaro, S., Curtiss, M., Davis, K., Deutschbauer, A., Entian, K. D., Flaherty, P., Foury, F., Garfinkel, D. J., Gerstein, M., Gotte, D., Guldener, U., Hegemann, J. H., Hempel, S., Herman, Z., Jaramillo, D. F., Kelly, D. E., Kelly, S. L., Kotter, P., LaBonte, D., Lamb, D. C., Lan, N., Liang, H., Liao, H., Liu, L., Luo, C., Lussier, M., Mao, R., Menard, P., Ooi, S. L., Revuelta, J. L., Roberts, C. J., Rose, M., Ross-Macdonald, P., Scherens, B., Schimmack, G., Shafer, B., Shoemaker, D. D., Sookhai-Mahadeo, S., Storms, R. K., Strathern, J. N., Valle, G., Voet, M., Volckaert, G., Wang, C. Y., Ward, T. R., Wilhelmy, J., Winzeler, E. A., Yang, Y., Yen, G., Youngman, E., Yu, K., Bussey, H., Boeke, J. D., Snyder, M., Philippsen, P., Davis, R. W. and Johnston, M. (2002). Functional profiling of the Saccharomyces cerevisiae genome. Nature 418, 387391.
Gitau, G. W., Mandal, P., Blatch, G. L., Przyborski, J. and Shonhai, A. (2012). Characterisation of the Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop). Cell Stress and Chaperones 17, 191202.
Harikishore, A., Niang, M., Rajan, S., Preiser, P. R. and Yoon, H. S. (2013). Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent. Scientific Reports 3, 2501.
Hieronymus, H., Lamb, J., Ross, K. N., Peng, X. P., Clement, C., Rodina, A., Nieto, M., Du, J., Stegmaier, K., Raj, S. M., Maloney, K. N., Clardy, J., Hahn, W. C., Chiosis, G. and Golub, T. R. (2006). Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell 10, 321330.
Hombach, A., Ommen, G., Chrobak, M. and Clos, J. (2012). The Hsp90-Sti1 interaction is critical for Leishmania donovani proliferation in both life cycle stages. Cellular Microbiology 15, 585600.
Johnson, J. L. and Brown, C. (2009). Plasticity of the Hsp90 chaperone machine in divergent eukaryotic organisms. Cell Stress and Chaperones 14, 8394.
Johnson, J. L. and Toft, D. O. (1995). Binding of p23 and hsp90 during assembly with the progesterone receptor. Molecular Endocrinology 9, 670678.
Kadota, Y., Amigues, B., Ducassou, L., Madaoui, H., Ochsenbein, F., Guerois, R. and Shirasu, K. (2008). Structural and functional analysis of SGT1-HSP90 core complex required for innate immunity in plants. EMBO Reports 9, 12091215.
Kadota, Y., Shirasu, K. and Guerois, R. (2010). NLR sensors meet at the SGT1-HSP90 crossroad. Trends in Biochemical Sciences 35, 199207.
Kimura, Y., Rutherford, S. L., Miyata, Y., Yahara, I., Freeman, B. C., Yue, L., Morimoto, R. I. and Lindquist, S. (1997). Cdc37 is a molecular chaperone with specific functions in signal transduction. Genes and Development 11, 17751785.
Ko, H. S., Bailey, R., Smith, W. W., Liu, Z., Shin, J. H., Lee, Y. I., Zhang, Y. J., Jiang, H., Ross, C. A., Moore, D. J., Patterson, C., Petrucelli, L., Dawson, T. M. and Dawson, V. L. (2009). CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proceedings of the National Academy of Sciences USA 106, 28972902.
Kosano, H., Stensgard, B., Charlesworth, M. C., McMahon, N. and Toft, D. (1998). The assembly of progesterone receptor-hsp90 complexes using purified proteins. Journal of Biological Chemistry 273, 3297332979.
Kotaka, M., Ye, H., Alag, R., Hu, G., Bozdech, Z., Preiser, P. R., Yoon, H. S. and Lescar, J. (2008). Crystal structure of the FK506 binding domain of Plasmodium falciparum FKBP35 in complex with FK506. Biochemistry 47, 59515961.
Kumar, R., Musiyenko, A. and Barik, S. (2003). The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin. Malaria Journal 2, 30.
Kumar, R., Adams, B., Musiyenko, A., Shulyayeva, O. and Barik, S. (2005). The FK506-binding protein of the malaria parasite, Plasmodium falciparum, is a FK506-sensitive chaperone with FK506-independent calcineurin-inhibitory activity. Molecular and Biochemical Parasitology 141, 163173.
Kumar, R., Pavithra, S. R. and Tatu, U. (2007). Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria. Journal of Biosciences 32, 531536.
Kundrat, L. and Regan, L. (2010). Balance between folding and degradation for Hsp90-dependent client proteins: a key role for CHIP. Biochemistry 49, 74287438.
LaCount, D. J., Vignali, M., Chettier, R., Phansalkar, A., Bell, R., Hesselberth, J. R., Schoenfeld, L. W., Ota, I., Sahasrabudhe, S., Kurschner, C., Fields, S. and Hughes, R. E. (2005). A protein interaction network of the malaria parasite Plasmodium falciparum . Nature 438, 103107.
Lamphere, L., Fiore, F., Xu, X., Brizuela, L., Keezer, S., Sardet, C., Draetta, G. F. and Gyuris, J. (1997). Interaction between Cdc37 and Cdk4 in human cells. Oncogene 14, 19992004.
Laufen, T., Mayer, M. P., Beisel, C., Klostermeier, D., Mogk, A., Reinstein, J. and Bukau, B. (1999). Mechanism of regulation of hsp70 chaperones by DnaJ cochaperones. Proceedings of the National Academy of Sciences USA 96, 54525457.
Lee, Y. T., Jacob, J., Michowski, W., Nowotny, M., Kuznicki, J. and Chazin, W. J. (2004). Human Sgt1 binds HSP90 through the CHORD-Sgt1 domain and not the tetratricopeptide repeat domain. Journal of Biological Chemistry 279, 1651116517.
Li, J., Richter, K. and Buchner, J. (2011). Mixed Hsp90-cochaperone complexes are important for the progression of the reaction cycle. Nature Structural and Molecular Biology 18, 6166.
Li, J., Soroka, J. and Buchner, J. (2012). The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperones. Biochimica et Biophysica Acta 1823, 624635.
Liu, J., Istvan, E. S., Gluzman, I. Y., Gross, J. and Goldberg, D. E. (2006). Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proceedings of the National Academy of Sciences USA 103, 88408845.
MacKinnon, S., Durst, T., Arnason, J. T., Angerhofer, C., Pezzuto, J., Sanchez-Vindas, P. E., Poveda, L. J. and Gbeassor, M. (1997). Antimalarial activity of tropical Meliaceae extracts and gedunin derivatives. Journal of Natural Products 60, 336341.
Mandal, A. K., Lee, P., Chen, J. A., Nillegoda, N., Heller, A., DiStasio, S., Oen, H., Victor, J., Nair, D. M., Brodsky, J. L. and Caplan, A. J. (2007). Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation. Journal of Cell Biology 176, 319328.
Marsh, J. A., Kalton, H. M. and Gaber, R. F. (1998). Cns1 is an essential protein associated with the hsp90 chaperone complex in Saccharomyces cerevisiae that can restore cyclophilin 40-dependent functions in cpr7Delta cells. Molecular and Cellular Biology 18, 73537359.
Matts, R. L., Brandt, G. E., Lu, Y., Dixit, A., Mollapour, M., Wang, S., Donnelly, A. C., Neckers, L., Verkhivker, G. and Blagg, B. S. (2011). A systematic protocol for the characterization of Hsp90 modulators. Bioorganic and Medicinal Chemistry 19, 684692.
Mayor, A., Martinon, F., De Smedt, T., Petrilli, V. and Tschopp, J. (2007). A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nature Immunology 8, 497503.
McDonough, H. and Patterson, C. (2003). CHIP: a link between the chaperone and proteasome systems. Cell Stress and Chaperones 8, 303308.
McLaughlin, S. H., Sobott, F., Yao, Z. P., Zhang, W., Nielsen, P. R., Grossmann, J. G., Laue, E. D., Robinson, C. V. and Jackson, S. E. (2006). The co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins. Journal of Molecular Biology 356, 746758.
Monaghan, P. and Bell, A. (2005). A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities. Molecular and Biochemical Parasitology 139, 185195.
Morales, M. A., Watanabe, R., Dacher, M., Chafey, P., Osorio y Fortea, J., Scott, D. A., Beverley, S. M., Ommen, G., Clos, J., Hem, S., Lenormand, P., Rousselle, J. C., Namane, A. and Spath, G. F. (2010). Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage. Proceedings of the National Academy of Sciences USA 107, 83818386.
Muller, P., Ruckova, E., Halada, P., Coates, P. J., Hrstka, R., Lane, D. P. and Vojtesek, B. (2013). C-terminal phosphorylation of Hsp70 and Hsp90 regulates alternate binding to co-chaperones CHIP and HOP to determine cellular protein folding/degradation balances. Oncogene 32, 31013110.
Murata, S., Minami, Y., Minami, M., Chiba, T. and Tanaka, K. (2001). CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Reports 2, 11331138.
Muskett, P. and Parker, J. (2003). Role of SGT1 in the regulation of plant R gene signalling. Microbes and Infection 5, 969976.
Owens-Grillo, J. K., Czar, M. J., Hutchison, K. A., Hoffmann, K., Perdew, G. H. and Pratt, W. B. (1996). A model of protein targeting mediated by immunophilins and other proteins that bind to hsp90 via tetratricopeptide repeat domains. Journal of Biological Chemistry 271, 1346813475.
Pallavi, R., Acharya, P., Chandran, S., Daily, J. P. and Tatu, U. (2010 a). Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients. Malaria Journal 9, 236.
Pallavi, R., Roy, N., Nageshan, R. K., Talukdar, P., Pavithra, S. R., Reddy, R., Venketesh, S., Kumar, R., Gupta, A. K., Singh, R. K., Yadav, S. C. and Tatu, U. (2010 b). Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. Journal of Biological Chemistry 285, 3796437975.
Patwardhan, C. A., Fauq, A., Peterson, L. B., Miller, C., Blagg, B. S. and Chadli, A. (2013). Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. Journal of Biological Chemistry 288, 73137325.
Pavithra, S. R., Banumathy, G., Joy, O., Singh, V. and Tatu, U. (2004). Recurrent fever promotes Plasmodium falciparum development in human erythrocytes. Journal of Biological Chemistry 279, 4669246699.
Pavithra, S. R., Kumar, R. and Tatu, U. (2007). Systems analysis of chaperone networks in the malarial parasite Plasmodium falciparum . PLoS Comput Biol 3, 17011715.
Perdew, G. H., Wiegand, H., Vanden Heuvel, J. P., Mitchell, C. and Singh, S. S. (1997). A 50 kilodalton protein associated with raf and pp60(v-src) protein kinases is a mammalian homolog of the cell cycle control protein cdc37. Biochemistry 36, 36003607.
Pesce, E. R., Cockburn, I. L., Goble, J. L., Stephens, L. L. and Blatch, G. L. (2010). Malaria heat shock proteins: drug targets that chaperone other drug targets. Infectious Disorders Drug Targets 10, 147157.
Petersen, I., Eastman, R. and Lanzer, M. (2011). Drug-resistant malaria: molecular mechanisms and implications for public health. FEBS Letters 585, 15511562.
Picard, D. (2006). Intracellular dynamics of the Hsp90 co-chaperone p23 is dictated by Hsp90. Experimental Cell Research 312, 198204.
Piper, P. W., Millson, S. H., Mollapour, M., Panaretou, B., Siligardi, G., Pearl, L. H. and Prodromou, C. (2003). Sensitivity to Hsp90-targeting drugs can arise with mutation to the Hsp90 chaperone, cochaperones and plasma membrane ATP binding cassette transporters of yeast. European Journal of Biochemistry 270, 46894695.
Pirkl, F. and Buchner, J. (2001). Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40. Journal of Molecular Biology 308, 795806.
Pratt, W. B. (1998). The hsp90-based chaperone system: involvement in signal transduction from a variety of hormone and growth factor receptors. Proceedings of the Society for Experimental Biology and Medicine 217, 420434.
Pratt, W. B. and Toft, D. O. (1997). Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocrine Reviews 18, 306360.
Prodromou, C. (2012). The ‘active life’ of Hsp90 complexes. Biochimica et Biophysica Acta 1823, 614623.
Prodromou, C., Siligardi, G., O'Brien, R., Woolfson, D. N., Regan, L., Panaretou, B., Ladbury, J. E., Piper, P. W. and Pearl, L. H. (1999). Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. EMBO Journal 18, 754762.
Prodromou, C., Panaretou, B., Chohan, S., Siligardi, G., O'Brien, R., Ladbury, J. E., Roe, S. M., Piper, P. W. and Pearl, L. H. (2000). The ATPase cycle of Hsp90 drives a molecular ‘clamp’ via transient dimerization of the N-terminal domains. EMBO Journal 19, 43834392.
Ratajczak, T., Ward, B. K., Cluning, C. and Allan, R. K. (2009). Cyclophilin 40: an Hsp90-cochaperone associated with apo-steroid receptors. International Journal of Biochemistry and Cell Biology, 41, 16521655.
Rochani, A. K., Singh, M. and Tatu, U. (2013). Heat shock protein 90 inhibitors as broad spectrum anti-infectives. Current Pharmaceutical Design 19, 377386.
Rosenthal, P. J. (2004). Cysteine proteases of malaria parasites. International Journal for Parasitology 34, 14891499.
Russell, R., Wali Karzai, A., Mehl, A. F. and McMacken, R. (1999). DnaJ dramatically stimulates ATP hydrolysis by DnaK: insight into targeting of Hsp70 proteins to polypeptide substrates. Biochemistry 38, 41654176.
Shonhai, A. (2010). Plasmodial heat shock proteins: targets for chemotherapy. FEMS Immunology and Medical Microbiology 58, 6174.
Silverstein, A. M., Galigniana, M. D., Chen, M. S., Owens-Grillo, J. K., Chinkers, M. and Pratt, W. B. (1997). Protein phosphatase 5 is a major component of glucocorticoid receptor hsp90 complexes with properties of an FK506-binding immunophilin. Journal of Biological Chemistry 272, 1622416230.
Stavreva, D. A., Muller, W. G., Hager, G. L., Smith, C. L. and McNally, J. G. (2004). Rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomes. Molecular and Cellular Biology 24, 26822697.
Storer, C. L., Dickey, C. A., Galigniana, M. D., Rein, T. and Cox, M. B. (2011). FKBP51 and FKBP52 in signaling and disease. Trends in Endocrinology and Metabolism 22, 481490.
Sullivan, W., Stensgard, B., Caucutt, G., Bartha, B., McMahon, N., Alnemri, E. S., Litwack, G. and Toft, D. (1997). Nucleotides and two functional states of hsp90. Journal of Biological Chemistry 272, 80078012.
Sullivan, W. P., Owen, B. A. and Toft, D. O. (2002). The influence of ATP and p23 on the conformation of hsp90. Journal of Biological Chemistry 277, 4594245948.
Taipale, M., Jarosz, D. F. and Lindquist, S. (2010). HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nature Reviews: Molecular Cell Biology 11, 515528.
Takahashi, A., Casais, C., Ichimura, K. and Shirasu, K. (2003). HSP90 interacts with RAR1 and SGT1 and is essential for RPS2-mediated disease resistance in Arabidopsis. Proceedings of the National Academy of Sciences USA 100, 1177711782.
Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M. and Kudo, I. (2000). Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. Journal of Biological Chemistry 275, 3277532782.
Tapia, H. and Morano, K. A. (2010). Hsp90 nuclear accumulation in quiescence is linked to chaperone function and spore development in yeast. Molecular Biology of the Cell 21, 6372.
Vaughan, A. M. and Kappe, S. H. (2012). Malaria vaccine development: persistent challenges. Current Opinion in Immunology 24, 324331.
Vaughan, C. K., Mollapour, M., Smith, J. R., Truman, A., Hu, B., Good, V. M., Panaretou, B., Neckers, L., Clarke, P. A., Workman, P., Piper, P. W., Prodromou, C. and Pearl, L. H. (2008). Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Molecular Cell 31, 886895.
Wandinger, S. K., Suhre, M. H., Wegele, H. and Buchner, J. (2006). The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90. EMBO Journal 25, 367376.
Ward, P., Equinet, L., Packer, J. and Doerig, C. (2004). Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote. BMC Genomics 5, 79.
Wiser, M. F. (2003). A Plasmodium homologue of cochaperone p23 and its differential expression during the replicative cycle of the malaria parasite. Parasitology Research 90, 166170.
Wiser, M. F. and Plitt, B. (1987). Plasmodium berghei, P. chabaudi, and P. falciparum: similarities in phosphoproteins and protein kinase activities and their stage specific expression. Experimental Parasitology 64, 328335.
Wongsrichanalai, C. and Meshnick, S. R. (2008). Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia–Thailand border. Emerging Infectious Diseases 14, 716719.
World Health Organization (2012). World Malaria Report 2012. World Health Organization, Geneva, Switzerland.
Zhang, M., Boter, M., Li, K., Kadota, Y., Panaretou, B., Prodromou, C., Shirasu, K. and Pearl, L. H. (2008). Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein complexes. EMBO Journal 27, 27892798.
Zhang, T., Li, Y., Yu, Y., Zou, P., Jiang, Y. and Sun, D. (2009). Characterization of celastrol to inhibit hsp90 and cdc37 interaction. Journal of Biological Chemistry 284, 3538135389.
Zhao, R. and Houry, W. A. (2005). Hsp90: a chaperone for protein folding and gene regulation. Biochemistry and Cell Biology, 83, 703710.
Zhao, R., Kakihara, Y., Gribun, A., Huen, J., Yang, G., Khanna, M., Costanzo, M., Brost, R. L., Boone, C., Hughes, T. R., Yip, C. M. and Houry, W. A. (2008). Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation. Journal of Cell Biology 180, 563578.
Zuehlke, A. D. and Johnson, J. L. (2012). Chaperoning the chaperone: a role for the co-chaperone Cpr7 in modulating Hsp90 function in Saccharomyces cerevisiae . Genetics 191, 805814.
Zurawska, A., Urbanski, J., Matuliene, J., Baraniak, J., Klejman, M. P., Filipek, S., Matulis, D. and Bieganowski, P. (2010). Mutations that increase both Hsp90 ATPase activity in vitro and Hsp90 drug resistance in vivo . Biochimica et Biophysica Acta 1803, 575583.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 3
Total number of PDF views: 37 *
Loading metrics...

Abstract views

Total abstract views: 240 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 17th March 2018. This data will be updated every 24 hours.