Publikationsserver der Universitätsbibliothek Marburg
Titel:A destabilisation domain approach to define the in vivo functional importance of PfHsp70-1 and PfHsp40 in the intraerythrocytic life cycle of Plasmodium falciparum
Autor:Mandal, Pradipta
Weitere Beteiligte: Przyborski, Jude (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0659
DOI: https://doi.org/10.17192/z2017.0659
URN: urn:nbn:de:hebis:04-z2017-06590
DDC:570 Biowissenschaften, Biologie
Titel (trans.):Destabilisierungsdomänen Ansatz zur Definition der in vivo funktionalen Bedeutung von PfHsp70-1 und PfHsp40 für den intraerythrozytischen Lebenszyklus von P. falciparum.
Publikationsdatum:2019-10-16
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
PFB0595w, PfHsp40PfHsp70-1

Summary:
The apicomplexan malaria parasite, Plasmodium falciparum is capable of invading red blood cells and causes the most virulent form of malaria. The life cycle of P. falciparum involves the migration from the poikilothermic mosquito vector to warm-blooded human host and vice versa. Such transition introduces radical differences between the cellular environments where the parasite resides, imposing physiological stress. The diverse environmental insults in addition to the febrile fever episodes imparts challenge on the proteostasis, resulting in the evolutionary selection of a diverse network of molecular chaperones. In fact, some molecular chaperones are essential for the survival of Plasmodium. Due to the developing resistance of Plasmodium against currently available drugs, heat shock proteins have received extensive research attention as antimalarial targets in recent years. Plasmodium codes for one Hsp90 homologue and a constitutively expressed heat inducible cytosolic Hsp70 known as PfHsp70-1. In general, Hsp70 interacts with co-chaperone Hsp40 initiating the protein folding machinery that finally interacts with Hsp90 to maintain proteostasis in a cell. PfHsp90 has been found to be essential for the intraerythrocytic development of P. falciparum. Although there have been some in vitro studies on the biology of PfHsp70-1, the information on the in vivo essential function of PfHsp70-1 and its interaction with PfHsp40 is limited. In this study, we wanted to identify the in vivo biological importance of PfHsp70-1 and one of its predicted co-chaperones, PfHsp40 by the overexpression of the dominant negative alleles tagged to recently characterised destabilisation domain (dd) to regulate protein level. We expressed a dominant negative PfHsp70-1 possessing a point mutation (E187K), severely affecting normal domain movement important for its function. PfHsp40 was mutated in the conserved HPD motif (D34N) necessary for establishing interaction with PfHsp70-1. Unfortunately, we could not obtain sufficient overexpression of the episomal dominant negative versions to override the function of the endogenous proteins in a competitive manner. The cellular levels of endogenous proteins were higher by several folds compared to that of the episomally expressed dominant negative alleles. The destabilisation strategy has been reported to be successful for studying certain plasmodial proteins. But in contrast, during our work the level of almost none of the candidate chaperones could be controlled by either FKBP or E. coli DHFR derived destabilisation domains in a ligand dependent fashion. Although, the level of wild type PfHsp70-1 could be regulated by this strategy, the dominant negative version with only one amino acid substitution made it non responsive to dd tagging and further ligand treatment. At the same time, the level of control proteins could be efficiently regulated by stabilising ligands. Recently, success of destabilization domain strategy for conditional knockdown of several genes has been reported. But in contrast, our observations in this study unravel the possible drawbacks. We assume that the success of such an approach is greatly protein dependent. Based on the several reports initially this approach appeared to be the most beneficial system. But, the failure to successfully implement this strategy demands careful consideration in selecting an alternative future approach to study the function of essential genes in Plasmodium.

Bibliographie / References

  1. RAMYA, T. N., KARMODIYA, K., SUROLIA, A. & SUROLIA, N. 2007. 15- deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum. J Biol Chem, 282, 6388-97.
  2. RUSSO, I., OKSMAN, A., VAUPEL, B. & GOLDBERG, D. E. 2009. A calpain unique to alveolates is essential in Plasmodium falciparum and its knockdown reveals an involvement in pre-S-phase development. Proc Natl Acad Sci U S A, 106, 1554-9.
  3. VAN DIJK, M. R., JANSE, C. J., THOMPSON, J., WATERS, A. P., BRAKS, J. A., DODEMONT, H. J., STUNNENBERG, H. G., VAN GEMERT, G. J., SAUERWEIN, R. W. & ELING, W. 2001. A central role for P48/45 in malaria parasite male gamete fertility. Cell, 104, 153-64.
  4. TARDIEUX, I., BAINES, I., MOSSAKOWSKA, M. & WARD, G. E. 1998. Actin-binding proteins of invasive malaria parasites and the regulation of actin polymerization by a complex of 32/34-kDa proteins associated with heat shock protein 70kDa. Mol Biochem Parasitol, 93, 295-308.
  5. TAVARIA, M., GABRIELE, T., KOLA, I. & ANDERSON, R. L. 1996. A hitchhiker's guide to the human Hsp70 family. Cell Stress Chaperones, 1, 23-8.
  6. MA, Y. F., WEISS, L. M. & HUANG, H. 2012. A method for rapid regulation of protein expression in Trypanosoma cruzi. Int J Parasitol, 42, 33-7.
  7. RITOSSA, F. 1962. A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia, 18, 571-573.
  8. RIDLEY, R. G. 2002. Introduction. Antimalarial drug resistance: ramifications, explanations and challenges. Microbes Infect, 4, 155-6.
  9. UHLEMANN, A. C. & KRISHNA, S. 2005. Antimalarial multi-drug resistance in Asia: mechanisms and assessment. Curr Top Microbiol Immunol, 295, 39-53.
  10. WISER, M. F. 2003. A Plasmodium homologue of cochaperone p23 and its differential expression during the replicative cycle of the malaria parasite. Parasitol Res, 90, 166- 70.
  11. SILVA, M. D., COOKE, B. M., GUILLOTTE, M., BUCKINGHAM, D. W., SAUZET, J. P., LE SCANF, C., CONTAMIN, H., DAVID, P., MERCEREAU-PUIJALON, O. & BONNEFOY, S. 2005. A role for the Plasmodium falciparum RESA protein in resistance against heat shock demonstrated using gene disruption. Mol Microbiol, 56, 990-1003.
  12. MURALIDHARAN, V., OKSMAN, A., IWAMOTO, M., WANDLESS, T. J. & GOLDBERG, D. E. 2011. Asparagine repeat function in a Plasmodium falciparum protein assessed via a regulatable fluorescent affinity tag. Proc Natl Acad Sci U S A, 108, 4411-6.
  13. SMITH, D. F., STENSGARD, B. A., WELCH, W. J. & TOFT, D. O. 1992. Assembly of progesterone receptor with heat shock proteins and receptor activation are ATP mediated events. J Biol Chem, 267, 1350-6.
  14. PINO, P., SEBASTIAN, S., KIM, E. A., BUSH, E., BROCHET, M., VOLKMANN, K., KOZLOWSKI, E., LLINAS, M., BILLKER, O. & SOLDATI-FAVRE, D. 2012. A tetracycline-repressible transactivator system to study essential genes in malaria parasites. Cell Host Microbe, 12, 824-34.
  15. PRUDENCIO, M., MOTA, M. M. & MENDES, A. M. 2011. A toolbox to study liver stage malaria. Trends Parasitol, 27, 565-74.
  16. PALLAVI, R., ACHARYA, P., CHANDRAN, S., DAILY, J. P. & TATU, U. 2010. Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients. Malar J, 9, 236.
  17. VIITANEN, P. V., LUBBEN, T. H., REED, J., GOLOUBINOFF, P., O'KEEFE, D. P. & LORIMER, G. H. 1990. Chaperonin-facilitated refolding of ribulosebisphosphate carboxylase and ATP hydrolysis by chaperonin 60 (groEL) are K+ dependent. Biochemistry, 29, 5665-71.
  18. TATAR, M., KHAZAELI, A. A. & CURTSINGER, J. W. 1997. Chaperoning extended life. Nature, 390, 30.
  19. NOLLEN, E. A. & MORIMOTO, R. I. 2002. Chaperoning signaling pathways: molecular chaperones as stress-sensing 'heat shock' proteins. J Cell Sci, 115, 2809-16.
  20. RANFORD, J. C., COATES, A. R. & HENDERSON, B. 2000. Chaperonins are cellsignalling proteins: the unfolding biology of molecular chaperones. Expert Rev Mol Med, 2, 1-17.
  21. GITAU,! G.! W.,! MANDAL,! P .,! BLATCH,! G.! L.,! PRZYBORSKI,! J.! &! SHONHAI,! A.! 2012.! Characterisation!of!the!Plasmodium!falciparum!Hsp70NHsp90!organising!protein! (PfHop).!Cell$Stress$Chaperones,!17,!191N202.
  22. WELLEMS, T. E. & PLOWE, C. V. 2001. Chloroquine-resistant malaria. J Infect Dis, 184, 770-6.
  23. WATANABE, J. 1997. Cloning and characterization of heat shock protein DnaJ homologues from Plasmodium falciparum and comparison with ring infected erythrocyte surface antigen. Mol Biochem Parasitol, 88, 253-8.
  24. SYIN, C. & GOLDMAN, N. D. 1996. Cloning of a Plasmodium falciparum gene related to the human 60-kDa heat shock protein. Mol Biochem Parasitol, 79, 13-9.
  25. SQUIRES, C. L., PEDERSEN, S., ROSS, B. M. & SQUIRES, C. 1991. ClpB is the Escherichia coli heat shock protein F84.1. J Bacteriol, 173, 4254-62.
  26. MELKI, R., BATELIER, G., SOULIE, S. & WILLIAMS, R. C., JR. 1997. Cytoplasmic chaperonin containing TCP-1: structural and functional characterization. Biochemistry, 36, 5817-26.
  27. NICOLL, W. S., BOTHA, M., MCNAMARA, C., SCHLANGE, M., PESCE, E. R., BOSHOFF, A., LUDEWIG, M. H., ZIMMERMANN, R., CHEETHAM, M. E., CHAPPLE, J. P. & BLATCH, G. L. 2007. Cytosolic and ER J-domains of mammalian and parasitic origin can functionally interact with DnaK. Int J Biochem Cell Biol, 39, 736-51.
  28. TARCSA, E. & FESUS, L. 1990. Determination of epsilon (gamma-glutamyl)lysine crosslink in proteins using phenylisothiocyanate derivatization and high-pressure liquid chromatographic separation. Anal Biochem, 186, 135-40.
  29. RITOSSA, F. 1996. Discovery of the heat shock response. Cell Stress Chaperones, 1, 97-8.
  30. SCHRODER, H., LANGER, T., HARTL, F. U. & BUKAU, B. 1993. DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J, 12, 4137-44.
  31. STRAUS, D., WALTER, W. & GROSS, C. A. 1990. DnaK, DnaJ, and GrpE heat shock proteins negatively regulate heat shock gene expression by controlling the synthesis and stability of sigma 32. Genes Dev, 4, 2202-9.
  32. SHEPPARD, D. 1994. Dominant negative mutants: tools for the study of protein function in vitro and in vivo. Am J Respir Cell Mol Biol, 11, 1-6.
  33. SMITH, D. F. 1993. Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. Mol Endocrinol, 7, 1418- 29.
  34. TOWBIN, H., STAEHELIN, T. & GORDON, J. 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A, 76, 4350-4.
  35. PHYO, A. P., NKHOMA, S., STEPNIEWSKA, K., ASHLEY, E. A., NAIR, S., MCGREADY, R., LER MOO, C., AL-SAAI, S., DONDORP, A. M., LWIN, K. M., SINGHASIVANON, P., DAY, N. P., WHITE, N. J., ANDERSON, T. J. & NOSTEN, F. 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet, 379, 1960-6.
  36. LIBEREK, K., MARSZALEK, J., ANG, D., GEORGOPOULOS, C. & ZYLICZ, M. 1991. Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Natl Acad Sci U S A, 88, 2874-8.
  37. PAEK, K. H. & WALKER, G. C. 1987. Escherichia coli dnaK null mutants are inviable at high temperature. J Bacteriol, 169, 283-90.
  38. VANBOGELEN, R. A., ABSHIRE, K. Z., MOLDOVER, B., OLSON, E. R. & NEIDHARDT, F. C. 1997. Escherichia coli proteome analysis using the gene-protein database. Electrophoresis, 18, 1243-51.
  39. SNOW, R. W., CRAIG, M., DEICHMANN, U. & MARSH, K. 1999. Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. Bull World Health Organ, 77, 624-40.
  40. RAKHIT, R., EDWARDS, S. R., IWAMOTO, M. & WANDLESS, T. J. 2011. Evaluation of FKBP and DHFR based destabilizing domains in Saccharomyces cerevisiae. Bioorg Med Chem Lett, 21, 4965-8.
  41. LUM, R., TKACH, J. M., VIERLING, E. & GLOVER, J. R. 2004. Evidence for an unfolding/threading mechanism for protein disaggregation by Saccharomyces cerevisiae Hsp104. J Biol Chem, 279, 29139-46.
  42. NOEDL, H., SE, Y., SCHAECHER, K., SMITH, B. L., SOCHEAT, D., FUKUDA, M. M. & ARTEMISININ RESISTANCE IN CAMBODIA 1 STUDY, C. 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med, 359, 2619-20.
  43. SMITH, D. L. & DOERDER, F. P. 1992. Exceptions to mutual exclusion among cell surface i-antigens of Tetrahymena thermophila during salt stress and stationary phase. J Protozool, 39, 628-35.
  44. MAIER, A. G., RUG, M., O'NEILL, M. T., BROWN, M., CHAKRAVORTY, S., SZESTAK, T., CHESSON, J., WU, Y., HUGHES, K., COPPEL, R. L., NEWBOLD, C., BEESON, J. G., CRAIG, A., CRABB, B. S. & COWMAN, A. F. 2008. Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell, 134, 48-61.
  45. SILVA, N. M., GAZZINELLI, R. T., SILVA, D. A., FERRO, E. A., KASPER, L. H. & MINEO, J. R. 1998. Expression of Toxoplasma gondii-specific heat shock protein 70 during In vivo conversion of bradyzoites to tachyzoites. Infect Immun, 66, 3959-63.
  46. MCCARTHY, C. B., SANTINI, M. S., PIMENTA, P. F. & DIAMBRA, L. A. 2013. First comparative transcriptomic analysis of wild adult male and female Lutzomyia longipalpis, vector of visceral leishmaniasis. PLoS One, 8, e58645.
  47. PINO, P. 2013. From technology to biology: a malaria genetic toolbox for the functional dissection of essential genes. Mol Microbiol, 88, 650-4.
  48. O'NEILL, M. T., PHUONG, T., HEALER, J., RICHARD, D. & COWMAN, A. F. 2011. Gene deletion from Plasmodium falciparum using FLP and Cre recombinases: implications for applied site-specific recombination. Int J Parasitol, 41, 117-23.
  49. VAN DIJK, M. R., DOURADINHA, B., FRANKE-FAYARD, B., HEUSSLER, V., VAN DOOREN, M. W., VAN SCHAIJK, B., VAN GEMERT, G. J., SAUERWEIN, R. W., MOTA, M. M., WATERS, A. P. & JANSE, C. J. 2005. Genetically attenuated, P36pdeficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proc Natl Acad Sci U S A, 102, 12194-9.
  50. PETERS, A. L. & VAN NOORDEN, C. J. 2009. Glucose-6-phosphate dehydrogenase deficiency and malaria: cytochemical detection of heterozygous G6PD deficiency in women. J Histochem Cytochem, 57, 1003-11.
  51. RYE, H. S., ROSEMAN, A. M., CHEN, S., FURTAK, K., FENTON, W. A., SAIBIL, H. R. & HORWICH, A. L. 1999. GroEL-GroES cycling: ATP and nonnative polypeptide direct alternation of folding-active rings. Cell, 97, 325-38.
  52. UENO, T., TAGUCHI, H., TADAKUMA, H., YOSHIDA, M. & FUNATSU, T. 2004. GroEL mediates protein folding with a two successive timer mechanism. Mol Cell, 14, 423-34.
  53. WIESGIGL, M. & CLOS, J. 2001. Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovani. Mol Biol Cell, 12, 3307-16.
  54. SCHLESINGER, M. J. 1990. Heat shock proteins. J Biol Chem, 265, 12111-4.
  55. MACARIO, A. J. 1995. Heat-shock proteins and molecular chaperones: implications for pathogenesis, diagnostics, and therapeutics. Int J Clin Lab Res, 25, 59-70.
  56. SOTI, C., NAGY, E., GIRICZ, Z., VIGH, L., CSERMELY, P. & FERDINANDY, P. 2005. Heat shock proteins as emerging therapeutic targets. Br J Pharmacol, 146, 769-80.
  57. NEWPORT, G. R. 1991. Heat shock proteins as vaccine candidates. Semin Immunol, 3, 17- 24.
  58. POCKLEY, A. G. 2002. Heat shock proteins, inflammation, and cardiovascular disease. Circulation, 105, 1012-7.
  59. POCKLEY, A. G. 2001. Heat shock proteins in health and disease: therapeutic targets or therapeutic agents? Expert Rev Mol Med, 3, 1-21.
  60. POLLA, B. S. 1991. Heat shock proteins in host-parasite interactions. Immunol Today, 12, A38-41.
  61. WIECH, H., BUCHNER, J., ZIMMERMANN, M., ZIMMERMANN, R. & JAKOB, U. 1993. Hsc70, immunoglobulin heavy chain binding protein, and Hsp90 differ in their ability to stimulate transport of precursor proteins into mammalian microsomes. J Biol Chem, 268, 7414-21.
  62. POPIEL, H. A., TAKEUCHI, T., FUJITA, H., YAMAMOTO, K., ITO, C., YAMANE, H., MURAMATSU, S., TODA, T., WADA, K. & NAGAI, Y. 2012. Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism. PLoS One, 7, e51069.
  63. MISRA, G. & RAMACHANDRAN, R. 2009. Hsp70-1 from Plasmodium falciparum: protein stability, domain analysis and chaperone activity. Biophys Chem, 142, 55-64.
  64. MAYER, M. P. & BUKAU, B. 2005. Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci, 62, 670-84.
  65. MAYER, M. P. & BUKAU, B. 1998. Hsp70 chaperone systems: diversity of cellular functions and mechanism of action. Biol Chem, 379, 261-8.
  66. NJUNGE, J. M., LUDEWIG, M. H., BOSHOFF, A., PESCE, E. R. & BLATCH, G. L. 2013. Hsp70s and J proteins of Plasmodium parasites infecting rodents and primates: structure, function, clinical relevance, and drug targets. Curr Pharm Des, 19, 387- 403.
  67. YOUNG, J. C., MOAREFI, I. & HARTL, F. U. 2001. Hsp90: a specialized but essential protein-folding tool. J Cell Biol, 154, 267-73.
  68. TAIPALE, M., JAROSZ, D. F. & LINDQUIST, S. 2010. HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol, 11, 515-28.
  69. STERRENBERG, J. N., BLATCH, G. L. & EDKINS, A. L. 2011. Human DNAJ in cancer and stem cells. Cancer Lett, 312, 129-42.
  70. TRAGER, W. & JENSEN, J. B. 1976. Human malaria parasites in continuous culture. Science, 193, 673-5.
  71. SMITH, D. F., SULLIVAN, W. P., MARION, T. N., ZAITSU, K., MADDEN, B., MCCORMICK, D. J. & TOFT, D. O. 1993. Identification of a 60-kilodalton stressrelated protein, p60, which interacts with hsp90 and hsp70. Mol Cell Biol, 13, 869-76.
  72. WIRTZ, E. & CLAYTON, C. 1995. Inducible gene expression in trypanosomes mediated by a prokaryotic repressor. Science, 268, 1179-83.
  73. PARSELL, D. A. & SAUER, R. T. 1989. Induction of a heat shock-like response by unfolded protein in Escherichia coli: dependence on protein level not protein degradation. Genes Dev, 3, 1226-32.
  74. MAKINO, M., UEMURA, N., MORODA, M., KIKUMURA, A., PIAO, L. X., MOHAMED, R. M. & AOSAI, F. 2011. Innate immunity in DNA vaccine with Toxoplasma gondiiheat shock protein 70 gene that induces DC activation and Th1 polarization. Vaccine, 29, 1899-905.
  75. NYALWIDHE, J., MAIER, U. G. & LINGELBACH, K. 2003. Intracellular parasitism: cell biological adaptations of parasitic protozoa to a life inside cells. Zoology (Jena), 106, 341-8.
  76. SHONHAI, A., MAIER, A. G., PRZYBORSKI, J. M. & BLATCH, G. L. 2011. Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis. Protein Pept Lett, 18, 143-57.
  77. SCHIRMER, R. H., ADLER, H., PICKHARDT, M. & MANDELKOW, E. 2011. "Lest we forget you--methylene blue...". Neurobiol Aging, 32, 2325 e7-16.
  78. TOMOYASU, T., OGURA, T., TATSUTA, T. & BUKAU, B. 1998. Levels of DnaK and DnaJ provide tight control of heat shock gene expression and protein repair in Escherichia coli. Mol Microbiol, 30, 567-81.
  79. SARGEANT, T. J., MARTI, M., CALER, E., CARLTON, J. M., SIMPSON, K., SPEED, T. P. & COWMAN, A. F. 2006. Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites. Genome Biol, 7, R12.
  80. MAIER, A. G., COOKE, B. M., COWMAN, A. F. & TILLEY, L. 2009. Malaria parasite proteins that remodel the host erythrocyte. Nat Rev Microbiol, 7, 341-54.
  81. OHTSUKA, K. & HATA, M. 2000. Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. Cell Stress Chaperones, 5, 98-112.
  82. LANZER, M., WICKERT, H., KROHNE, G., VINCENSINI, L. & BRAUN BRETON, C. 2006. Maurer's clefts: a novel multi-functional organelle in the cytoplasm of Plasmodium falciparum-infected erythrocytes. Int J Parasitol, 36, 23-36.
  83. LAUFEN, T., MAYER, M. P., BEISEL, C., KLOSTERMEIER, D., MOGK, A., REINSTEIN, J. & BUKAU, B. 1999. Mechanism of regulation of hsp70 chaperones by DnaJ cochaperones. Proc Natl Acad Sci U S A, 96, 5452-7.
  84. MOTA, M. M., PRADEL, G., VANDERBERG, J. P., HAFALLA, J. C., FREVERT, U., NUSSENZWEIG, R. S., NUSSENZWEIG, V. & RODRIGUEZ, A. 2001. Migration of Plasmodium sporozoites through cells before infection. Science, 291, 141-4.
  85. MEISSNER, M., BRECHT, S., BUJARD, H. & SOLDATI, D. 2001. Modulation of myosin A expression by a newly established tetracycline repressor-based inducible system in Toxoplasma gondii. Nucleic Acids Res, 29, E115.
  86. ROEPE, P. D. 2009. Molecular and physiologic basis of quinoline drug resistance in Plasmodium falciparum malaria. Future Microbiol, 4, 441-55.
  87. SMITH, D. F., WHITESELL, L. & KATSANIS, E. 1998. Molecular chaperones: biology and prospects for pharmacological intervention. Pharmacol Rev, 50, 493-514.
  88. SAMBROOK J, R. D. 2001. Molecular Cloning: A laboratory manual. Cold spring Harbor Laboratory Press.
  89. MEISSNER, M., BREINICH, M. S., GILSON, P. R. & CRABB, B. S. 2007. Molecular genetic tools in Toxoplasma and Plasmodium: achievements and future needs. Curr Opin Microbiol, 10, 349-56.
  90. SUGIYAMA, Y., SUZUKI, A., KISHIKAWA, M., AKUTSU, R., HIROSE, T., WAYE, M. M., TSUI, S. K., YOSHIDA, S. & OHNO, S. 2000. Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation. J Biol Chem, 275, 1095-104.
  91. MOSENSON, J. A., ZLOZA, A., NIELAND, J. D., GARRETT-MAYER, E., EBY, J. M., HUELSMANN, E. J., KUMAR, P., DENMAN, C. J., LACEK, A. T., KOHLHAPP, F. J., ALAMIRI, A., HUGHES, T., BINES, S. D., KAUFMAN, H. L., OVERBECK, A., MEHROTRA, S., HERNANDEZ, C., NISHIMURA, M. I., GUEVARAPATINO, J. A. & LE POOLE, I. C. 2013. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci Transl Med, 5, 174ra28.
  92. NG, O. T., OOI, E. E., LEE, C. C., LEE, P. J., NG, L. C., PEI, S. W., TU, T. M., LOH, J. P. & LEO, Y. S. 2008. Naturally acquired human Plasmodium knowlesi infection, Singapore. Emerg Infect Dis, 14, 814-6.
  93. ZHAO, R., DAVEY, M., HSU, Y. C., KAPLANEK, P., TONG, A., PARSONS, A. B., KROGAN, N., CAGNEY, G., MAI, D., GREENBLATT, J., BOONE, C., EMILI, A. & HOURY, W. A. 2005. Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone. Cell, 120, 715-27.
  94. MORANO, K. A. 2007. New tricks for an old dog: the evolving world of Hsp70. Ann N Y Acad Sci, 1113, 1-14.
  95. MEDEMA, R. H. 2004. Optimizing RNA interference for application in mammalian cells. Biochem J, 380, 593-603.
  96. MATAMBO, T. S., ODUNUGA, O. O., BOSHOFF, A. & BLATCH, G. L. 2004. Overproduction, purification, and characterization of the Plasmodium falciparum heat shock protein 70. Protein Expr Purif, 33, 214-22.
  97. RUSSO, I., BABBITT, S., MURALIDHARAN, V., BUTLER, T., OKSMAN, A. & GOLDBERG, D. E. 2010. Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte. Nature, 463, 632-6.
  98. SHONHAI, A. 2010. Plasmodial heat shock proteins: targets for chemotherapy. FEMS Immunol Med Microbiol, 58, 61-74.
  99. KULZER, S., CHARNAUD, S., DAGAN, T., RIEDEL, J., MANDAL, P., PESCE, E. R., BLATCH, G. L., CRABB, B. S., GILSON, P. R. & PRZYBORSKI, J. M. 2012. Plasmodium falciparum-encoded exported hsp70/hsp40 chaperone/co-chaperone complexes within the host erythrocyte. Cell Microbiol, 14, 1784-95.
  100. SHONHAI, A., BOSHOFF, A. & BLATCH, G. L. 2005. Plasmodium falciparum heat shock protein 70 is able to suppress the thermosensitivity of an Escherichia coli DnaK mutant strain. Mol Genet Genomics, 274, 70-8.
  101. VYTHILINGAM, I., NOORAZIAN, Y. M., HUAT, T. C., JIRAM, A. I., YUSRI, Y. M., AZAHARI, A. H., NORPARINA, I., NOORRAIN, A. & LOKMANHAKIM, S. 2008. Plasmodium knowlesi in humans, macaques and mosquitoes in peninsular Malaysia. Parasit Vectors, 1, 26.
  102. NYALWIDHE, J. & LINGELBACH, K. 2006. Proteases and chaperones are the most abundant proteins in the parasitophorous vacuole of Plasmodium falciparum-infected erythrocytes. Proteomics, 6, 1563-73.
  103. RUTHERFORD, S. L. & ZUKER, C. S. 1994. Protein folding and the regulation of signaling pathways. Cell, 79, 1129-32.
  104. YON, J. M. 2001. Protein folding: a perspective for biology, medicine and biotechnology. Braz J Med Biol Res, 34, 419-35.
  105. LUHESHI, L. M., CROWTHER, D. C. & DOBSON, C. M. 2008. Protein misfolding and disease: from the test tube to the organism. Curr Opin Chem Biol, 12, 25-31.
  106. TISSIERES, A., MITCHELL, H. K. & TRACY, U. M. 1974. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J Mol Biol, 84, 389-98.
  107. PRZYBORSKI, J. M. & LANZER, M. 2005. Protein transport and trafficking in Plasmodium falciparum-infected erythrocytes. Parasitology, 130, 373-88.
  108. VINCENSINI, L., RICHERT, S., BLISNICK, T., VAN DORSSELAER, A., LEIZEWAGNER, E., RABILLOUD, T. & BRAUN BRETON, C. 2005. Proteomic analysis identifies novel proteins of the Maurer's clefts, a secretory compartment delivering Plasmodium falciparum proteins to the surface of its host cell. Mol Cell Proteomics, 4, 582-93.
  109. PASINI, E. M., BRAKS, J. A., FONAGER, J., KLOP, O., AIME, E., SPACCAPELO, R., OTTO, T. D., BERRIMAN, M., HISS, J. A., THOMAS, A. W., MANN, M., JANSE, C. J., KOCKEN, C. H. & FRANKE-FAYARD, B. 2013. Proteomic and genetic analyses demonstrate that Plasmodium berghei blood stages export a large and diverse repertoire of proteins. Mol Cell Proteomics, 12, 426-48.
  110. SIBLEY, C. H., HYDE, J. E., SIMS, P. F., PLOWE, C. V., KUBLIN, J. G., MBERU, E. K., COWMAN, A. F., WINSTANLEY, P. A., WATKINS, W. M. & NZILA, A. M. 2001. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol, 17, 582-8.
  111. PAVITHRA, S. R., BANUMATHY, G., JOY, O., SINGH, V. & TATU, U. 2004. Recurrent fever promotes Plasmodium falciparum development in human erythrocytes. J Biol Chem, 279, 46692-9.
  112. MADEIRA DA SILVA, L., OWENS, K. L., MURTA, S. M. & BEVERLEY, S. M. 2009. Regulated expression of the Leishmania major surface virulence factor lipophosphoglycan using conditionally destabilized fusion proteins. Proc Natl Acad Sci U S A, 106, 7583-8.
  113. PRODROMOU, C., SILIGARDI, G., O'BRIEN, R., WOOLFSON, D. N., REGAN, L., PANARETOU, B., LADBURY, J. E., PIPER, P. W. & PEARL, L. H. 1999. Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain cochaperones. EMBO J, 18, 754-62.
  114. PRATT, W. B. & TOFT, D. O. 2003. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med (Maywood), 228, 111- 33.
  115. SILVER, J. T. & NOBLE, E. G. 2012. Regulation of survival gene hsp70. Cell Stress Chaperones, 17, 1-9.
  116. VAN SCHAIJK, B. C., VOS, M. W., JANSE, C. J., SAUERWEIN, R. W. & KHAN, S. M. 2010. Removal of heterologous sequences from Plasmodium falciparum mutants using FLPe-recombinase. PLoS One, 5, e15121.
  117. LIM, J. I., BLAIR, N. P. & LIU, S. J. 1990. Retinal pigment epithelium tear in a diabetic patient with exudative retinal detachment following panretinal photocoagulation and filtration surgery. Arch Ophthalmol, 108, 173-4.
  118. ULLU, E., TSCHUDI, C. & CHAKRABORTY, T. 2004. RNA interference in protozoan parasites. Cell Microbiol, 6, 509-19.
  119. WHITE, A. D., HUANG, W. & JIANG, S. 2012. Role of nonspecific interactions in molecular chaperones through model-based bioinformatics. Biophys J, 103, 2484-91.
  120. MEISSNER, M., SCHLUTER, D. & SOLDATI, D. 2002. Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science, 298, 837-40.
  121. PASVOL, G., WILSON, R. J., SMALLEY, M. E. & BROWN, J. 1978. Separation of viable schizont-infected red cells of Plasmodium falciparum from human blood. Ann Trop Med Parasitol, 72, 87-8.
  122. MARTI, M., BAUM, J., RUG, M., TILLEY, L. & COWMAN, A. F. 2005. Signal-mediated export of proteins from the malaria parasite to the host erythrocyte. J Cell Biol, 171, 587-92.
  123. MCMILLAN, P. J., MILLET, C., BATINOVIC, S., MAIORCA, M., HANSSEN, E., KENNY, S., MUHLE, R. A., MELCHER, M., FIDOCK, D. A., SMITH, J. D., DIXON, M. W. & TILLEY, L. 2013. Spatial and temporal mapping of the PfEMP1 export pathway in Plasmodium falciparum. Cell Microbiol.
  124. MULLIS, K., FALOONA, F., SCHARF, S., SAIKI, R., HORN, G. & ERLICH, H. 1986. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol, 51 Pt 1, 263-73.
  125. MACARIO, A. J. & CONWAY DE MACARIO, E. 2000. Stress and molecular chaperones in disease. Int J Clin Lab Res, 30, 49-66.
  126. LAMB, J. R., BAL, V., MENDEZ-SAMPERIO, P., MEHLERT, A., SO, A., ROTHBARD, J., JINDAL, S., YOUNG, R. A. & YOUNG, D. B. 1989. Stress proteins may provide a link between the immune response to infection and autoimmunity. Int Immunol, 1, 191-6.
  127. PEARL, L. H. & PRODROMOU, C. 2000. Structure and in vivo function of Hsp90. Curr Opin Struct Biol, 10, 46-51.
  128. SHONHAI, A., BOTHA, M., DE BEER, T. A., BOSHOFF, A. & BLATCH, G. L. 2008. Structure-function study of a Plasmodium falciparum Hsp70 using three dimensional modelling and in vitro analyses. Protein Pept Lett, 15, 1117-25.
  129. SCHEUFLER, C., BRINKER, A., BOURENKOV, G., PEGORARO, S., MORODER, L., BARTUNIK, H., HARTL, F. U. & MOAREFI, I. 2000. Structure of TPR domainpeptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell, 101, 199-210.
  130. SHEMETOV, A. A., SEIT-NEBI, A. S. & GUSEV, N. B. 2008. Structure, properties, and functions of the human small heat-shock protein HSP22 (HspB8, H11, E2IG1): a critical review. J Neurosci Res, 86, 264-9.
  131. WEGELE, H., WANDINGER, S. K., SCHMID, A. B., REINSTEIN, J. & BUCHNER, J. 2006. Substrate transfer from the chaperone Hsp70 to Hsp90. J Mol Biol, 356, 802- 11.
  132. LANGER, T., LU, C., ECHOLS, H., FLANAGAN, J., HAYER, M. K. & HARTL, F. U. 1992. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperonemediated protein folding. Nature, 356, 683-9.
  133. LAMBROS, C. & VANDERBERG, J. P. 1979. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol, 65, 418-20.
  134. PAVITHRA, S. R., KUMAR, R. & TATU, U. 2007. Systems analysis of chaperone networks in the malarial parasite Plasmodium falciparum. PLoS Comput Biol, 3, 1701-15.
  135. MAHALINGAM, D., SWORDS, R., CAREW, J. S., NAWROCKI, S. T., BHALLA, K. & GILES, F. J. 2009. Targeting HSP90 for cancer therapy. Br J Cancer, 100, 1523-9.
  136. MEISSNER, M., KREJANY, E., GILSON, P. R., DE KONING-WARD, T. F., SOLDATI, D. & CRABB, B. S. 2005. Tetracycline analogue-regulated transgene expression in Plasmodium falciparum blood stages using Toxoplasma gondii transactivators. Proc Natl Acad Sci U S A, 102, 2980-5.
  137. MCMILLAN, D. R., GETHING, M. J. & SAMBROOK, J. 1994. The cellular response to unfolded proteins: intercompartmental signaling. Curr Opin Biotechnol, 5, 540-5.
  138. MCLAUGHLIN, S. H., SOBOTT, F., YAO, Z. P., ZHANG, W., NIELSEN, P. R., GROSSMANN, J. G., LAUE, E. D., ROBINSON, C. V. & JACKSON, S. E. 2006. The co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins. J Mol Biol, 356, 746-58.
  139. SACHS, J. & MALANEY, P. 2002. The economic and social burden of malaria. Nature, 415, 680-5.
  140. SABBATANI, S., FIORINO, S. & MANFREDI, R. 2010. The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern? Braz J Infect Dis, 14, 299- 309.
  141. RUG, M. & MAIER, A. G. 2011. The heat shock protein 40 family of the malaria parasite Plasmodium falciparum. IUBMB Life, 63, 1081-6.
  142. RICHTER, K., HASLBECK, M. & BUCHNER, J. 2010. The heat shock response: life on the verge of death. Mol Cell, 40, 253-66.
  143. STRUB, A., ROTTGERS, K. & VOOS, W. 2002. The Hsp70 peptide-binding domain determines the interaction of the ATPase domain with Tim44 in mitochondria. EMBO J, 21, 2626-35.
  144. WANDINGER, S. K., RICHTER, K. & BUCHNER, J. 2008. The Hsp90 chaperone machinery. J Biol Chem, 283, 18473-7.
  145. LI, J., SOROKA, J. & BUCHNER, J. 2012. The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperones. Biochim Biophys Acta, 1823, 624-35.
  146. MORISHIMA, Y., KANELAKIS, K. C., MURPHY, P. J., LOWE, E. R., JENKINS, G. J., OSAWA, Y., SUNAHARA, R. K. & PRATT, W. B. 2003. The hsp90 cochaperone p23 is the limiting component of the multiprotein hsp90/hsp70-based chaperone system in vivo where it acts to stabilize the client protein: hsp90 complex. J Biol Chem, 278, 48754-63.
  147. MCCALLUM, C. D., DO, H., JOHNSON, A. E. & FRYDMAN, J. 2000. The interaction of the chaperonin tailless complex polypeptide 1 (TCP1) ring complex (TRiC) with ribosome-bound nascent chains examined using photo-cross-linking. J Cell Biol, 149, 591-602.
  148. LINGELBACH, K. & PRZYBORSKI, J. M. 2006. The long and winding road: protein trafficking mechanisms in the Plasmodium falciparum infected erythrocyte. Mol Biochem Parasitol, 147, 1-8.
  149. VAN DE KLUNDERT, F. A., SMULDERS, R. H., GIJSEN, M. L., LINDNER, R. A., JAENICKE, R., CARVER, J. A. & DE JONG, W. W. 1998. The mammalian small heat-shock protein Hsp20 forms dimers and is a poor chaperone. Eur J Biochem, 258, 1014-21.
  150. TOOVEY, S. 2004. The Miraculous Fever-Tree. The Cure that Changed the World Fiametta Rocco; Harper Collins, San Francisco, 2004, 348 pages, Paperback, ISBN 0-00- 6532357. Travel Med Infect Dis, 2, 109-10.
  151. ZEYMER, C., WERBECK, N. D., SCHLICHTING, I. & REINSTEIN, J. 2013. The molecular mechanism of Hsp100 chaperone inhibition by the prion curing agent guanidinium chloride. J Biol Chem, 288, 7065-76.
  152. LINGELBACH, K. & JOINER, K. A. 1998. The parasitophorous vacuole membrane surrounding Plasmodium and Toxoplasma: an unusual compartment in infected cells. J Cell Sci, 111 ( Pt 11), 1467-75.
  153. MILLER, L. H., BARUCH, D. I., MARSH, K. & DOUMBO, O. K. 2002. The pathogenic basis of malaria. Nature, 415, 673-9.
  154. PESCE, E. R., ACHARYA, P., TATU, U., NICOLL, W. S., SHONHAI, A., HOPPE, H. C. & BLATCH, G. L. 2008. The Plasmodium falciparum heat shock protein 40, Pfj4, associates with heat shock protein 70 and shows similar heat induction and localisation patterns. Int J Biochem Cell Biol, 40, 2914-26.
  155. MCCARTY, J. S., BUCHBERGER, A., REINSTEIN, J. & BUKAU, B. 1995. The role of ATP in the functional cycle of the DnaK chaperone system. J Mol Biol, 249, 126-37.
  156. LIU, J., GLUZMAN, I. Y., DREW, M. E. & GOLDBERG, D. E. 2005. The role of Plasmodium falciparum food vacuole plasmepsins. J Biol Chem, 280, 1432-7.
  157. THEYSSEN, H., SCHUSTER, H. P., PACKSCHIES, L., BUKAU, B. & REINSTEIN, J. 1996. The second step of ATP binding to DnaK induces peptide release. J Mol Biol, 263, 657-70.
  158. SHONHAI, A., BOSHOFF, A. & BLATCH, G. L. 2007. The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum. Protein Sci, 16, 1803-18.
  159. NZILA, A. M., MBERU, E. K., SULO, J., DAYO, H., WINSTANLEY, P. A., SIBLEY, C. H. & WATKINS, W. M. 2000. Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother, 44, 991-6.
  160. PLATTNER, F., YAROVINSKY, F., ROMERO, S., DIDRY, D., CARLIER, M. F., SHER, A. & SOLDATI-FAVRE, D. 2008. Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response. Cell Host Microbe, 3, 77-87.
  161. SOLDATI, D. & BOOTHROYD, J. C. 1993. Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii. Science, 260, 349-52.
  162. MAYER, R. J., ARNOLD, J., LASZLO, L., LANDON, M. & LOWE, J. 1991. Ubiquitin in health and disease. Biochim Biophys Acta, 1089, 141-57.
  163. ROSENZWEIG, R., MORADI, S., ZARRINE-AFSAR, A., GLOVER, J. R. & KAY, L. E. 2013. Unraveling the mechanism of protein disaggregation through a ClpB-DnaK interaction. Science, 339, 1080-3.
  164. ROSSNER, M. & YAMADA, K. M. 2004. What's in a picture? The temptation of image manipulation. J Cell Biol, 166, 11-5.
  165. WHO 2013. Malaria Fact Sheet. World Health Organisation.
  166. WHO 2012. World Malaria Report 2010. World Health Organisation.
  167. NIAD. 2012. Life Cycle of the Malaria Parasite [Online]. USA: National Institute of Health. Available: http://www.niaid.nih.gov/topics/Malaria/Pages/lifecycle.aspx [Accessed 11.07.2013.

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