Chaperone Proteins in Plasmodium falciparum Biology

Plasmodium falciparum relies on a sophisticated network of molecular chaperones to navigate the extreme environmental transitions between mosquito vector and human host. Central to this system are heat shock proteins (Hsps), notably Hsp70 and Hsp90 families, which safeguard the parasite’s proteome by promoting correct folding, preventing aggregation and facilitating refolding of stress-damaged polypeptides. A cohort of parasite-encoded co-chaperones, including J domain proteins (JDPs) and the Hsp70–Hsp90 organising protein (PfHop), orchestrates the specificity and timing of chaperone action. Unique isoforms such as PfHsp70-x and PfHsp70-z contribute to host-cell remodelling by supporting exportome functions that mediate cytoadherence and immune evasion. This exportome, comprising parasite proteins translocated into the erythrocyte cytosol, is vital for virulence and survival in the circulatory milieu. Structural variations in the nucleotide-binding and substrate-binding domains of Plasmodium Hsps relative to their human counterparts present opportunities for selective drug targeting. Emerging evidence also links metabolic factors, such as polyamine levels, to chaperone regulation. Collectively, these insights underscore the global significance of chaperone systems as nodes of parasite adaptability and as attractive targets for novel antimalarial strategies.

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Chaperone Proteins in Plasmodium falciparum Biology publication trend

The graph below shows the total number of articles in chaperone proteins in plasmodium falciparum biology across all publications each year (not limited to Nature Index journals).

Technical terms

Molecular chaperone: A protein that assists in the folding, assembly and stabilisation of other proteins without being part of the final structure.

Heat shock protein (Hsp): A class of chaperones induced by thermal or oxidative stress to maintain protein homeostasis.

Co-chaperone: A regulatory protein that binds to chaperones, modulating their client specificity and ATPase cycle.

J domain protein (JDP): A co-chaperone bearing a conserved J domain that stimulates Hsp70 ATPase activity and client delivery.

Proteostasis: The cellular processes that control protein synthesis, folding, translocation and degradation to maintain functional integrity.

Exportome: The set of parasite proteins exported into the host erythrocyte to modify its membrane and cytoskeleton for cytoadherence.

References

1. An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection in Plasmodium falciparum and Proliferating Cells in Various Organisms. Molecules (2023).
2. In silico identification of modulators of J domain protein-Hsp70 interactions in Plasmodium falciparum: a drug repurposing strategy against malaria. Frontiers in Molecular Biosciences (2023).
3. Partners in Mischief: Functional Networks of Heat Shock Proteins of Plasmodium falciparum and Their Influence on Parasite Virulence. Biomolecules (2019).
4. Comparative structure-function features of Hsp70s of Plasmodium falciparum and human origins. Biophysical Reviews (2019).
5. The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites. PLOS ONE (2017).
6. Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity. PLOS ONE (2015).
7. Overexpression, Purification and Characterisation of the Plasmodium falciparum Hsp70-z (PfHsp70-z) Protein. PLOS ONE (2015).