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Plasmodium falciparum protein 'PfJ23' hosts distinct binding sites for major virulence factor 'PfEMP1' and Maurer's
Jasweer Kaur1, Vikash Kumar1, Amrit Pal Singh2
1Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, India.
Abstract:
Plasmodium falciparum (Pf) proteins exported to infected erythrocytes are key effectors of malaria pathogenesis. These include the PfEMP1 (Pf erythrocyte membrane protein 1) protein family that affects malaria-related mortality through cytoadhesion and parasite immune evasion. Parasites also induce membranous structures called Maurer's clefts (MC) in infected erythrocytes to compensate the lack of host protein synthetic and export machinery. PfEMP1 export is mediated by a myriad of proteins including Pf skeleton binding protein 1 (PfSBP1) and PF70, a hypothetical 16 family member. Here, we aim to understand the function of the only other exported PEXEL-positive hyp16 member 'PfJ23'. Our in vitro and in silico data suggest this protein to be mostly α-helical while displaying different oligomeric forms under reducing and non-reducing conditions. We show coherent expression, partial co-localization and direct interaction of purified PfSBP1 with recombinant and native PfJ23. Recombinant and parasite-expressed PfJ23 also bind to the cytoplasmic tail of PfEMP1, and they seem to partly co-localize during parasite development. Both novel binding partners interact simultaneously with PfJ23 in vitro to form a complex. Our results suggest a probable role for PfJ23 in export of PEXEL-negative proteins like PfSBP1 and PfEMP1, furthering our understanding of malaria biology.
Insights
Plasmodium falciparum J23 (PfJ23) protein interacts with PfEMP1 and PfSBP1, suggesting a role in exporting malaria pathogenesis proteins. This finding advances our understanding of malaria parasite biology and protein export mechanisms.
Area of Science:
- Malaria pathogenesis
- Protein export mechanisms
- Plasmodium falciparum biology
Background:
- Plasmodium falciparum (Pf) exports proteins to infected erythrocytes, crucial for malaria pathogenesis.
- PfEMP1 (Pf erythrocyte membrane protein 1) mediates cytoadhesion and immune evasion, impacting malaria mortality.
- Maurer's clefts (MC) are induced by parasites to aid protein export.
Purpose of the Study:
- To elucidate the function of PfJ23, an exported PEXEL-positive hyp16 family member.
- To investigate the interactions of PfJ23 with known export machinery components.
Main Methods:
- In vitro and in silico analyses of PfJ23 structure and oligomerization.
- Co-localization and interaction studies using purified and parasite-expressed proteins (PfSBP1, PfJ23, PfEMP1).
Main Results:
- PfJ23 is primarily alpha-helical and exhibits varied oligomeric states.
- PfJ23 directly interacts with PfSBP1 and binds to the cytoplasmic tail of PfEMP1.
- PfJ23, PfSBP1, and PfEMP1 form a complex, with partial co-localization observed.
Conclusions:
- PfJ23 likely plays a role in the export of PEXEL-negative proteins, including PfSBP1 and PfEMP1.
- This study reveals a novel interaction network in the malaria parasite's protein export pathway.
- Understanding PfJ23 function contributes to comprehending malaria pathogenesis and developing interventions.