4.7 Review

Hsp90 and Associated Co-Chaperones of the Malaria Parasite

Journal

BIOMOLECULES
Volume 12, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/biom12081018

Keywords

Plasmodium falciparum; heat shock proteins; cytosolic Hsp90; ATPase; co-chaperones; client proteins

Funding

  1. Higher Colleges of Technology, UAE (Interdisciplinary Research Grant, IRG)
  2. Rhodes University, South Africa (Rated Researcher Grant)
  3. Newton Advanced Fellowship from the Academy of Medical Sciences (UK)
  4. Royal Society (UK) [CHLnR1n180142]
  5. South African Research Chairs Initiative of the Department of Science and Technology (DST)
  6. NRF [98566]
  7. Rhodes University
  8. Bill and Melinda Gates Foundation
  9. Medicines for Malaria Venture [MMV]
  10. University of Cape Town Drug Discovery and Development Centre [H3D] [GCA/DD/rnd3/043]

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Heat shock protein 90 (Hsp90) plays an important role in cellular protein homeostasis. In parasitic protozoans, such as Plasmodium falciparum, Hsp90 and its associated co-chaperones have unique properties and functions. Understanding these differences may lead to the development of drugs to combat malaria.
Heat shock protein 90 (Hsp90) is one of the major guardians of cellular protein homeostasis, through its specialized molecular chaperone properties. While Hsp90 has been extensively studied in many prokaryotic and higher eukaryotic model organisms, its structural, functional, and biological properties in parasitic protozoans are less well defined. Hsp90 collaborates with a wide range of co-chaperones that fine-tune its protein folding pathway. Co-chaperones play many roles in the regulation of Hsp90, including selective targeting of client proteins, and the modulation of its ATPase activity, conformational changes, and post-translational modifications. Plasmodium falciparum is responsible for the most lethal form of human malaria. The survival of the malaria parasite inside the host and the vector depends on the action of molecular chaperones. The major cytosolic P. falciparum Hsp90 (PfHsp90) is known to play an essential role in the development of the parasite, particularly during the intra-erythrocytic stage in the human host. Although PfHsp90 shares significant sequence and structural similarity with human Hsp90, it has several major structural and functional differences. Furthermore, its co-chaperone network appears to be substantially different to that of the human host, with the potential absence of a key homolog. Indeed, PfHsp90 and its interface with co-chaperones represent potential drug targets for antimalarial drug discovery. In this review, we critically summarize the current understanding of the properties of Hsp90, and the associated co-chaperones of the malaria parasite.

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