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Published on: September 18, 2018
Plasmodium falciparum ring-infected erythrocyte surface antigen 3 (PfRESA3) is a cytoskeleton-interacting protein and
Nipa Rani Mallick1, Welka Sahu1, Deepak Kumar Ojha1
1School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha, India.
Abstract:
Plasmodium falciparum exports proteins into host erythrocytes for survival, but the roles of many of these proteins remain unexplored. Here, we used recombinant protein constructs and antibodies corresponding to Plasmodium falciparum ring-infected erythrocyte surface antigen-3 (PfRESA3) to identify it as a dense granule merozoite protein exported early to the inner erythrocyte membrane, where it associates with the cytoskeleton. Constructs lacking the J domain bound inside-out vesicles, implicating PRESAN and DnaJ-X in cytoskeletal interactions. Recombinant PfRESA3 constructs stimulated the ATPase activity of human HsHSPA8 and enhanced malate dehydrogenase (MDH) refolding. However, truncated PfRESA3 constructs did not significantly enhance MDH refolding by HsHSPA8. These findings suggest PfRESA3 modulates host HsHSPA8 to support cytoskeletal remodeling/parasite protein folding early in infection. Impact statement Our study uncovers a high-stakes hijacking of the human erythrocyte by Plasmodium falciparum. By identifying PfRESA3 as a potential co-chaperone that anchors to the host's cytoskeleton and recruits human chaperones, this study reveals a sophisticated survival strategy. It exposes a critical vulnerability in the parasite's early development inside the human erythrocyte.
Insights
Plasmodium falciparum uses PfRESA3 to hijack host cells, anchoring to the erythrocyte cytoskeleton and recruiting human chaperones. This reveals a sophisticated survival strategy and a vulnerability in early parasite development.
Area of Science:
- Malariology
- Cell Biology
- Protein Biochemistry
Background:
- Plasmodium falciparum exports proteins into host erythrocytes for survival.
- The functions of many exported proteins are unknown.
- PfRESA3 is a dense granule merozoite protein exported early in infection.
Purpose of the Study:
- To investigate the role of Plasmodium falciparum ring-infected erythrocyte surface antigen-3 (PfRESA3).
- To determine PfRESA3's interaction with the host erythrocyte cytoskeleton.
- To elucidate PfRESA3's effect on host chaperone activity.
Main Methods:
- Used recombinant protein constructs and antibodies for PfRESA3.
- Investigated protein interactions with erythrocyte vesicles and cytoskeleton.
- Assayed ATPase activity of human HsHSPA8 and malate dehydrogenase (MDH) refolding.
Main Results:
- PfRESA3 localizes to the inner erythrocyte membrane and associates with the cytoskeleton.
- The J domain of PfRESA3 is crucial for cytoskeletal interactions.
- PfRESA3 stimulates HsHSPA8 ATPase activity and enhances MDH refolding.
Conclusions:
- PfRESA3 acts as a co-chaperone, modulating host HsHSPA8.
- PfRESA3 supports cytoskeletal remodeling and protein folding during early infection.
- This represents a sophisticated parasite survival strategy and a potential therapeutic target.
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