Comparative Characterization of Plasmodium falciparum Hsp70-1 Relative to E. coli DnaK Reveals the Functional Specificity of the Parasite Chaperone

Biomolecules. 2020 Jun 4;10(6):856. doi: 10.3390/biom10060856.


Hsp70 is a conserved molecular chaperone. How Hsp70 exhibits specialized functions across species remains to be understood. Plasmodium falciparum Hsp70-1 (PfHsp70-1) and Escherichia coli DnaK are cytosol localized molecular chaperones that are important for the survival of these two organisms. In the current study, we investigated comparative structure-function features of PfHsp70-1 relative to DnaK and a chimeric protein, KPf, constituted by the ATPase domain of DnaK and the substrate binding domain (SBD) of PfHsp70-1. Recombinant forms of the three Hsp70s exhibited similar secondary and tertiary structural folds. However, compared to DnaK, both KPf and PfHsp70-1 were more stable to heat stress and exhibited higher basal ATPase activity. In addition, PfHsp70-1 preferentially bound to asparagine rich peptide substrates, as opposed to DnaK. Recombinant P. falciparum adenosylmethionine decarboxylase (PfAdoMetDC) co-expressed in E. coli with either KPf or PfHsp70-1 was produced as a fully folded product. Co-expression of PfAdoMetDC with heterologous DnaK in E. coli did not promote folding of the former. However, a combination of supplementary GroEL plus DnaK improved folding of PfAdoMetDC. These findings demonstrated that the SBD of PfHsp70-1 regulates several functional features of the protein and that this molecular chaperone is tailored to facilitate folding of plasmodial proteins.

Keywords: Hsp70; Plasmodium falciparum; chaperone function; co-expression; specificity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP72 Heat-Shock Proteins / chemistry
  • HSP72 Heat-Shock Proteins / metabolism*
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism*
  • Plasmodium falciparum / chemistry*
  • Plasmodium falciparum / metabolism
  • Protein Domains


  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • HSP72 Heat-Shock Proteins
  • Molecular Chaperones
  • dnaK protein, E coli