期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms22042226
关键词
malaria; Plasmodium falciparum; chaperone; GGMP repeats; Hsp70; Hop
资金
- Deutsche Forchungsgemeinshaft (DFG) under the theme, German-African Cooperation Projects in Infectiology [L1/402/14-1]
- Department of Science and Technology/National Research Foundation (NRF) of South Africa equipment grant [75464]
- NRF mobility grant [92598]
- African-German Network of Excellence in Science junior researcher grant
The GGMP motif in the cytosol-localized chaperone Hsp70-1 of Plasmodium falciparum plays a crucial role in the chaperone function and ATPase activity of the chimeric protein, as well as in its interaction with peptide substrates and co-chaperones. This motif contributes to the specialized chaperone function and high catalytic efficiency of PfHsp70-1.
Parasitic organisms especially those of the Apicomplexan phylum, harbour a cytosol localised canonical Hsp70 chaperone. One of the defining features of this protein is the presence of GGMP repeat residues sandwiched between alpha-helical lid and C-terminal EEVD motif. The role of the GGMP repeats of Hsp70s remains unknown. In the current study, we introduced GGMP mutations in the cytosol localised Hsp70-1 of Plasmodium falciparum (PfHsp70-1) and a chimeric protein (KPf), constituted by the ATPase domain of E. coli DnaK fused to the C-terminal substrate binding domain of PfHsp70-1. A complementation assay conducted using E. coli dnaK756 cells demonstrated that the GGMP motif was essential for chaperone function of the chimeric protein, KPf. Interestingly, insertion of GGMP motif of PfHsp70-1 into DnaK led to a lethal phenotype in E. coli dnaK756 cells exposed to elevated growth temperature. Using biochemical and biophysical assays, we established that the GGMP motif accounts for the elevated basal ATPase activity of PfHsp70-1. Furthermore, we demonstrated that this motif is important for interaction of the chaperone with peptide substrate and a co-chaperone, PfHop. Our findings suggest that the GGMP may account for both the specialised chaperone function and reportedly high catalytic efficiency of PfHsp70-1.
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