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An Exported Heat Shock Protein 40 Associates with Pathogenesis-Related Knobs in Plasmodium falciparum Infected Erythrocytes

By Pragyan Acharya, Shweta Chaubey, Manish Grover and Utpal Tatu

Abstract

Cell surface structures termed knobs are one of the most important pathogenesis related protein complexes deployed by the malaria parasite Plasmodium falciparum at the surface of the infected erythrocyte. Despite their relevance to the disease, their structure, mechanisms of traffic and their process of assembly remain poorly understood. In this study, we have explored the possible role of a parasite-encoded Hsp40 class of chaperone, namely PFB0090c/PF3D7_0201800 (KAHsp40) in protein trafficking in the infected erythrocyte. We found the gene coding for PF3D7_0201800 to be located in a chromosomal cluster together with knob components KAHRP and PfEMP3. Like the knob components, KAHsp40 too showed the presence of PEXEL motif required for transport to the erythrocyte compartment. Indeed, sub-cellular fractionation and immunofluorescence analysis (IFA) showed KAHsp40 to be exported in the erythrocyte cytoplasm in a stage dependent manner localizing as punctuate spots in the erythrocyte periphery, distinctly from Maurer's cleft, in structures which could be the reminiscent of knobs. Double IFA analysis revealed co-localization of PF3D7_0201800 with the markers of knobs (KAHRP, PfEMP1 and PfEMP3) and components of the PEXEL translocon (Hsp101, PTEX150). KAHsp40 was also found to be in a complex with KAHRP, PfEMP3 and Hsp101 as confirmed by co-immunoprecipitation assay. Our results suggest potential involvement of a parasite encoded Hsp40 in chaperoning knob assembly in the erythrocyte compartment

Topics: Biochemistry
Publisher: Public Library of Science
Year: 2012
DOI identifier: 10.1371/journal.pone.0044605
OAI identifier: oai:eprints.iisc.ernet.in:45199

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Citations

  1. (2008). A conditional export system provides new insights into protein export in Plasmodium falciparum-infected erythrocytes. doi
  2. (2004). A host-targeting signal in virulence proteins reveals a secretome in malarial infection. doi
  3. (2009). A newly discovered protein export machine in malaria parasites. doi
  4. (2007). Chaperoning a cellular upheaval in malaria: heat shock proteins in Plasmodium falciparum. doi
  5. (2008). Exported proteins required for virulence and rigidity of Plasmodium falciparuminfected human erythrocytes. doi
  6. (2006). Genesis of and trafficking to the Maurer’s clefts of Plasmodium falciparum-infected erythrocytes. doi
  7. (1976). Human malaria parasites in continuous culture. doi
  8. (2004). Hyper-expansion of asparagines correlates with an abundance of proteins with prion-like domains in Plasmodium falciparum. doi
  9. (2005). Maurer’s clefts-restricted localization, orientation and export of a Plasmodium falciparum RIFIN. doi
  10. (2006). Maurer’s clefts: a novel multi-functional organelle in the cytoplasm of Plasmodium falciparum- infected erythrocytes. doi
  11. (1996). Membrane knobs of unfixed Plasmodium falciparum infected erythrocytes: new findings as revealed by atomic force microscopy and surface potential spectroscopy. doi
  12. (2010). Parasiteencoded Hsp40 proteins define novel mobile structures in the cytosol of the P. falciparum- infected erythrocyte. doi
  13. (2000). Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin-spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton. doi
  14. (2009). Protein unfolding is an essential requirement for transport across the parasitophorous vacuolar membrane of Plasmodium falciparum. doi
  15. (1989). Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: evidence for membrane cycling from Golgi to ER. doi
  16. (2012). Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) intracellular domain reveals a conserved interaction epitope. doi
  17. (1989). Subtelomeric chromosome deletions in field isolates of Plasmodium falciparum and their relationship to loss of cytoadherence in vitro. doi
  18. (1997). Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress. Cell doi
  19. (2004). Targeting malaria virulence and remodelling proteins to the host erythrocyte.
  20. (2007). The Hsp40 proteins of Plasmodium falciparum and other apicomplexa: regulating chaperone power in the parasite and the host. doi
  21. (2007). The Hsp70 chaperone machines of Escherichia coli: a paradigm for the repartition of chaperone functions. doi
  22. (2004). The J-protein family: modulating protein assembly, disassembly and translocation. doi
  23. (1995). The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. doi
  24. (2006). The role of KAHRP domains in knob formation and cytoadherence of P. falciparuminfected human erythrocytes. doi
  25. (2007). The structural and functional diversity of doi
  26. (2008). The twists and turns of Maurer’s cleft trafficking in P. falciparum- infected erythrocytes. doi
  27. (2005). Trafficking determinants for PfEMP3 export and assembly under the Plasmodium falciparum-infected red blood cell membrane. doi

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